2,413 results on '"Théranostic"'
Search Results
252. Theranostic Options for Radioiodine-Refractory Differentiated Thyroid Carcinoma: Recent Advances, Challenges, and Road Ahead
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Swayamjeet Satapathy and Chandrasekhar Bal
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radioiodine-refractory differentiated thyroid cancer ,RAIR-DTC ,theranostic ,integrin binders ,RGD ,FAPI ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Radioiodine-refractory differentiated thyroid cancer (RAIR-DTC), though uncommon, presents a considerable therapeutic challenge with poor long-term outcomes. Currently, tyrosine kinase inhibitors are the mainstay of treatment for advanced RAIR-DTC patients. However, these agents are associated with a multitude of adverse events with resultant deterioration in the quality-of-life of the patients. Targeted theranostic approaches with radiolabelled integrin binders and fibroblast activation protein- (FAP)-inhibitors seem to have a promising role in the management of such patients. This mini-review focuses on these novel theranostic strategies in RAIR-DTC, with emphasis on recent advances, existing challenges, and future directions.
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- 2022
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253. Forging the Frontiers of Image-Guided Neurosurgery—The Emerging Uses of Theranostics in Neurosurgical Oncology
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Fred C. Lam, Uyanga Tsedev, Ekkehard M. Kasper, and Angela M. Belcher
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theranostic ,neurosurgery ,fluorescence-guide surgery ,nanotechnology ,NIR imaging in vivo ,Biotechnology ,TP248.13-248.65 - Published
- 2022
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254. Magnetic vortex nanoring coated with gadolinium oxide for highly enhanced T1-T2 dual-modality magnetic resonance imaging-guided magnetic hyperthermia cancer ablation
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Jianfeng Bao, Shuangshuang Guo, Xiangyang Zu, Yuchuan Zhuang, Dandan Fan, Yong Zhang, Yupeng Shi, Xin Pang, Zhenyu Ji, and Jingliang Cheng
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T1-T2 dual-modality ,Vortex nanoring ,MRI ,Magnetic hyperthermia ,Theranostic ,Tumor ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Nowadays, about 30% of magnetic resonance imaging (MRI) exams need contrast agents (CAs) to improve the sensitivity and quality of the images for accurate diagnosis. Here, a multifunctional nano-agent with ring-like vortex-domain iron oxide as core and gadolinium oxide as shell (vortex nanoring Fe3O4 @Gd2O3, abbreviated as VNFG) was firstly designed and prepared for highly enhanced T1-T2 dual-modality magnetic resonance imaging (MRI)-guided magnetic thermal cancer therapy. After thorough characterization, the core-shell structure of VNFG was confirmed. Moreover, the excellent heat generation property (SAR=984.26 W/g) of the proposed VNFG under alternating magnetic fields was firmly demonstrated. Furthermore, both in vitro and in vivo studies have revealed a good preliminary indication of VNFG’s biological compatibility, dual-modality enhancing feature and antitumor efficacy. This work demonstrates that the proposed VNFG can be a high-performance tumor diagnosis and theranostic treatment agent and may have great potential for clinical application in the future.
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- 2022
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255. Theranostic F-SLOH mitigates Alzheimer's disease pathology involving TFEB and ameliorates cognitive functions in Alzheimer's disease models
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Ashok Iyaswamy, Xueli Wang, Senthilkumar Krishnamoorthi, Venkatapathy Kaliamoorthy, Sravan G. Sreenivasmurthy, Siva Sundara Kumar Durairajan, Ju-Xian Song, Benjamin Chun-kit Tong, Zhou Zhu, Cheng-Fu Su, Jia Liu, King-Ho Cheung, Jia-Hong Lu, Jie-Qiong Tan, Hung Wing Li, Man Shing Wong, and Min Li
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Theranostic ,Alzheimer's disease ,Aβ-targeting ,Aβ-aggregate inhibition ,3XTg-AD ,5XFAD ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Accumulation of amyloid-β (Aβ) oligomers and phosphorylated Tau aggregates are crucial pathological events or factors that cause progressive neuronal loss, and cognitive impairments in Alzheimer's disease (AD). Current medications for AD have failed to halt, much less reverse this neurodegenerative disorder; therefore, there is an urgent need for the development of effective and safe drugs for AD therapy. In the present study, the in vivo therapeutic efficacy of an Aβ-oligomer-targeted fluorescent probe, F-SLOH, was extensively investigated in 5XFAD and 3XTg-AD mouse models. We have shown that F-SLOH exhibits an efficient inhibitory activity against Aβ aggregation in vivo, and acts as an effective theranostic agent for the treatment of multiple neuropathological changes in AD mouse models. F-SLOH has been found to significantly reduce not only the levels of Aβ oligomers, Tau aggregates and plaques but also the levels of amyloid precursor protein (APP) and its metabolites via autophagy lysosomal degradation pathway (ALP) in the brains of 5XFAD and 3XTg-AD mice. It also reduces astrocyte activation and microgliosis ultimately alleviating neuro-inflammation. Furthermore, F-SLOH mitigates hyperphosphorylated Tau aggregates, synaptic deficits and ameliorates synaptic memory function, and cognitive impairment in AD mouse models. The mechanistic studies have shown that F-SLOH promotes the clearance of C-terminal fragment 15 (CTF15) of APP and Paired helical filaments of Tau (PHF1) in stable cell models via the activation of transcription factor EB (TFEB). Moreover, F-SLOH promotes ALP and lysosomal biogenesis for the clearance of soluble, insoluble Aβ, and phospho Tau. Our results unambiguously reveal effective etiological capabilities of theranostic F-SLOH to target and intervene multiple neuropathological changes in AD mouse models. Therefore, F-SLOH demonstrates tremendous therapeutic potential for treating AD in its early stage.
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- 2022
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256. A survivin-driven, tumor-activatable minicircle system for prostate cancer theranostics
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TianDuo Wang, Yuanxin Chen, David Goodale, Alison L. Allan, and John A. Ronald
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minicircle ,survivin ,tumour-activatable ,theranostic ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Gene vectors regulated by tumor-specific promoters to express transgenes specifically in cancer cells are an emerging approach for cancer diagnosis and treatment. Minicircles are shortened plasmids stripped of prokaryotic sequences that have potency and safety characteristics beneficial for clinical translation. Previously, we developed minicircles driven by the tumor-specific survivin promoter, which exhibits elevated transcriptional activity in aggressive cancers, to express a secreted reporter for blood-based cancer detection. Here we present the first activatable, cancer theranostic minicircle system featuring a pair of diagnostic and therapeutic minicircles expressing Gaussia luciferase for urine-based cancer detection or cytosine deaminase:uracil phosphoribosyltransferase for gene-directed enzyme prodrug therapy. Diagnostic minicircles revealed urinary reporter output related to cellular survivin levels. Notably, mice with aggressive prostate tumors exhibited significantly higher urine reporter activity than mice with non-aggressive tumors and healthy mice after intratumoral minicircle administration. Therapeutic minicircles displayed specific cytotoxicity in survivin-rich cancer cells and significantly attenuated growth of aggressive orthotopic prostate tumors in mice. Use of these minicircles together creates a theranostic system that can first identify individuals carrying aggressive prostate cancer via a urinary test, followed by stringent control of tumor progression in stratified individuals who carry high-risk prostate lesions.
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- 2021
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257. Redox responsive nanoparticle encapsulating black phosphorus quantum dots for cancer theranostics
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Haolin Chen, Zhiming Liu, Bo Wei, Jun Huang, Xinru You, Jingyang Zhang, Zhiling Yuan, Zhilie Tang, Zhouyi Guo, and Jun Wu
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Optical coherence tomography ,Black phosphorus ,Theranostic ,Photothermal ,Cancer therapy ,Materials of engineering and construction. Mechanics of materials ,TA401-492 ,Biology (General) ,QH301-705.5 - Abstract
Effective cancer treatment puts high demands for cancer theranostics. For cancer diagnostics, optical coherence tomography (OCT) technology (including photothermal optical coherence tomography (PT-OCT)) has been widely investigated since it induces changes in optical phase transitions in tissue through environmental changes (such as temperature change for PT-OCT). In this report, redox responsive nanoparticle encapsulating black phosphorus quantum dots was developed as a robust PT-OCT agent. Briefly, black phosphorus quantum dots (BPQDs) are incorporated into cysteine-based poly-(disulfide amide) (Cys-PDSA) to form stable and biodegradable nanoagent. The excellent photothermal feature allows BPQD/Cys-PDSA nanoparticles (NPs) as a novel contrast agent for high-resolution PT-OCT bioimaging. The Cys-PDSA can rapidly respond to glutathione and effectively release BPQDs and drugs in vitro and in vivo. And the obtained NPs exhibit excellent near-infrared (NIR) photothermal transduction efficiency and drug delivery capacity that can serve as novel therapeutic platform, with very low chemo drug dosage and side effects. Both of the polymer and BPQD are degradable, indicating this platform is a rare PT-OCT agent that is completely biodegradable. Overall, our research highlights a biodegradable and biocompatible black phosphorus-based nanoagent for both cancer diagnosis and therapy.
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- 2021
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258. 18Oxygen Substituted Nucleosides Combined with Proton Beam Therapy: Therapeutic Transmutation In Vitro
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Tyvin Rich, MD, Dongfeng Pan, PhD, Mahendra Chordia, PhD, Cynthia Keppel, PhD, David Beylin, MS, Pavel Stepanov, MS, Mira Jung, PhD, Dalong Pang, PhD, Scott Grindrod, PhD, and Anatoly Dritschilo, MD
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proton therapy ,oxygen-18 ,nucleoside ,positron emission tomography (pet) ,theranostic ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Nuclear and particle physics. Atomic energy. Radioactivity ,QC770-798 - Abstract
Purpose: Proton therapy precisely delivers radiation to cancers to cause damaging strand breaks to cellular DNA, kill malignant cells, and stop tumor growth. Therapeutic protons also generate short-lived activated nuclei of carbon, oxygen, and nitrogen atoms in patients as a result of atomic transmutations that are imaged by positron emission tomography (PET). We hypothesized that the transition of 18Oto 18Fin an 18O-substituted nucleoside irradiated with therapeutic protons may result in the potential for combined diagnosis and treatment for cancer with proton therapy. Materials and Methods: Reported here is a feasibility study with a therapeutic proton beam used to irradiate H218O to a dose of 10 Gy produced by an 85 MeV pristine Bragg peak. PET imaging initiated >45 minutes later showed an 18F decay signal with T1/2 of ~111 minutes. Results: The 18Oto 18F transmutation effect on cell survival was tested by exposing SQ20B squamous carcinoma cells to physiologic 18O-thymidine concentrations of 5 μM for 48 hours followed by 1- to 9-Gy graded doses of proton radiation given 24 hours later. Survival analyses show radiation sensitization with a dose modification factor (DMF) of 1.2. Conclusions: These data support the idea of therapeutic transmutation in vitro as a biochemical consequence of proton activation of 18Oto 18F in substituted thymidine enabling proton radiation enhancement in a cancer cell. 18O-substituted molecules that incorporate into cancer targets may hold promise for improving the therapeutic window of protons and can be evaluated further for postproton therapy PET imaging.
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- 2021
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259. Production, purification, and radiolabeling of the 203Pb/212Pb theranostic pair
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Brooke L. McNeil, Andrew K. H. Robertson, Winnie Fu, Hua Yang, Cornelia Hoehr, Caterina F. Ramogida, and Paul Schaffer
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Lead-212 ,Lead-203 ,Thorium-228 generator ,Thallium-203 ,Theranostic ,Cyclen ,Medical physics. Medical radiology. Nuclear medicine ,R895-920 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Abstract Background Lead-212 (212Pb, t1/2 = 10.6 h) and lead-203 (203Pb, t1/2 = 51.9 h) are an element-equivalent, or a matched theranostic radioisotope pair that show great potential for application in targeted radionuclide therapy (TRT) and single-photon emission computed tomography (SPECT), respectively. At TRIUMF we have produced both 203Pb and 212Pb using TRIUMF’s TR13 (13 MeV) and 500 MeV cyclotrons, and subsequently purified and evaluated both radioisotopes using a series of pyridine-modified DOTA analogues in comparison to the commercially available chelates DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and TCMC (1,4,7,10-tetraaza-1,4,7,10-tetra(2-carbamoylmethyl)cyclododecane). Results Proton irradiation (12.8 MeV) of natural and enriched thallium-203 (203Tl) targets gave 203Pb saturation yields of 134 ± 25 and 483 ± 3 MBq/μA, respectively. Thorium-228 (228Th, t1/2 = 1.9 y), a by-product of 232Th proton spallation on TRIUMF’s main 500 MeV beamline (beamline 1A, BL1A), was recovered to build a 228Th/212Pb generator with the ability to deliver up to 9–10 MBq of 212Pb daily. Both lead isotopes were purified via solid phase extraction chromatography (Pb resin), and isolated in an acetate form ([203/212Pb]Pb(OAc)2) suitable for direct radiolabeling of chelators and bioconjugates. A series of cyclen-based chelators (herein referred to as DOTA-1Py, -2Py, and -3Py) along with established chelates DOTA and TCMC were evaluated for their ability to complex both 203Pb and 212Pb. All chelates incorporated 212Pb/203Pb efficiently, with higher radiolabeling yields observed for the 212Pb-complexes. Conclusion The production of 203Pb and 212Pb was established using TRIUMF 13 MeV and 500 MeV cyclotrons, respectively. Both production methods provided radiometals suitable for subsequent radiolabeling reactions using known and novel chelates. Furthermore, the novel chelate DOTA-3Py may be a good candidate for biomolecule conjugation and further theranostic 212Pb/203Pb studies.
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- 2021
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260. Targeting of immune checkpoint regulator V-domain Ig suppressor of T-cell activation (VISTA) with 89Zr-labelled CI-8993.
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Burvenich, Ingrid Julienne Georgette, Wichmann, Christian Werner, McDonald, Alexander Franklin, Guo, Nancy, Rigopoulos, Angela, Huynh, Nhi, Vail, Mary, Allen, Stacey, O’Keefe, Graeme Joseph, Scott, Fiona Elizabeth, Soikes, Raul, Angelides, Steven, Roemeling, Reinhard von, and Scott, Andrew Mark
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IMMUNE checkpoint proteins , *T cells , *RADIOCHEMICAL purification , *POSITRON emission tomography , *MONOCLONAL antibodies , *CANCER patients , *URODYNAMICS , *LABORATORY mice - Abstract
Background: CI-8993 is a fully human IgG1κ monoclonal antibody (mAb) that binds specifically to immune checkpoint molecule VISTA (V-domain Ig suppressor of T-cell activation). Phase I safety has been established in patients with advanced cancer (NCT02671955). To determine the pharmacokinetics and biodistribution of CI-8993 in patients, we aimed to develop 89Zr-labelled CI-8993 and validate PET imaging and quantitation in preclinical models prior to a planned human bioimaging trial.CI-8993 and human isotype IgG1 control were conjugated to the metal ion chelator
p -isothiocyanatobenzyl-desferrioxamine (Df). Quality of conjugates were assessed by SE-HPLC, SDS-PAGE, and FACS. After radiolabelling with zirconium-89 (89Zr), radioconjugates were assessed for radiochemical purity, immunoreactivity, antigen binding affinity, and serum stability in vitro. [89Zr]Zr-Df-CI-8993 alone (1 mg/kg, 4.6 MBq) or in combination with 30 mg/kg unlabelled CI-8993, as well as isotype control [89Zr]Zr-Df-IgG1 (1 mg/kg, 4.6 MBq) were assessed in human VISTA knock-in female (C57BL/6 N-Vsirtm1.1(VSIR)Geno, huVISTA KI) or control C57BL/6 mice bearing syngeneic MB49 bladder cancer tumours; and in BALB/cnu /nu mice bearing pancreatic Capan-2 tumours.Stable constructs with an average chelator-to-antibody ratio of 1.81 were achieved. SDS-PAGE and SE-HPLC showed integrity of CI-8993 was maintained after conjugation; and ELISA indicated no impact of conjugation and radiolabelling on binding to human VISTA. PET imaging and biodistribution in MB49 tumour-bearing huVISTA KI female mice showed specific localisation of [89Zr]Zr-Df-CI-8993 to VISTA in spleen and tumour tissues expressing human VISTA. Specific tumour uptake was also demonstrated in Capan-2 xenografted BALB/cnu /nu mice.We radiolabelled and validated [89Zr]Zr-Df-CI-8993 for specific binding to huVISTA in vivo. Our results demonstrate that 89Zr-labelled CI-8993 is now suitable for targeting and imaging VISTA expression in human trials.Methods: CI-8993 is a fully human IgG1κ monoclonal antibody (mAb) that binds specifically to immune checkpoint molecule VISTA (V-domain Ig suppressor of T-cell activation). Phase I safety has been established in patients with advanced cancer (NCT02671955). To determine the pharmacokinetics and biodistribution of CI-8993 in patients, we aimed to develop 89Zr-labelled CI-8993 and validate PET imaging and quantitation in preclinical models prior to a planned human bioimaging trial.CI-8993 and human isotype IgG1 control were conjugated to the metal ion chelatorp -isothiocyanatobenzyl-desferrioxamine (Df). Quality of conjugates were assessed by SE-HPLC, SDS-PAGE, and FACS. After radiolabelling with zirconium-89 (89Zr), radioconjugates were assessed for radiochemical purity, immunoreactivity, antigen binding affinity, and serum stability in vitro. [89Zr]Zr-Df-CI-8993 alone (1 mg/kg, 4.6 MBq) or in combination with 30 mg/kg unlabelled CI-8993, as well as isotype control [89Zr]Zr-Df-IgG1 (1 mg/kg, 4.6 MBq) were assessed in human VISTA knock-in female (C57BL/6 N-Vsirtm1.1(VSIR)Geno, huVISTA KI) or control C57BL/6 mice bearing syngeneic MB49 bladder cancer tumours; and in BALB/cnu /nu mice bearing pancreatic Capan-2 tumours.Stable constructs with an average chelator-to-antibody ratio of 1.81 were achieved. SDS-PAGE and SE-HPLC showed integrity of CI-8993 was maintained after conjugation; and ELISA indicated no impact of conjugation and radiolabelling on binding to human VISTA. PET imaging and biodistribution in MB49 tumour-bearing huVISTA KI female mice showed specific localisation of [89Zr]Zr-Df-CI-8993 to VISTA in spleen and tumour tissues expressing human VISTA. Specific tumour uptake was also demonstrated in Capan-2 xenografted BALB/cnu /nu mice.We radiolabelled and validated [89Zr]Zr-Df-CI-8993 for specific binding to huVISTA in vivo. Our results demonstrate that 89Zr-labelled CI-8993 is now suitable for targeting and imaging VISTA expression in human trials.Results: CI-8993 is a fully human IgG1κ monoclonal antibody (mAb) that binds specifically to immune checkpoint molecule VISTA (V-domain Ig suppressor of T-cell activation). Phase I safety has been established in patients with advanced cancer (NCT02671955). To determine the pharmacokinetics and biodistribution of CI-8993 in patients, we aimed to develop 89Zr-labelled CI-8993 and validate PET imaging and quantitation in preclinical models prior to a planned human bioimaging trial.CI-8993 and human isotype IgG1 control were conjugated to the metal ion chelatorp -isothiocyanatobenzyl-desferrioxamine (Df). Quality of conjugates were assessed by SE-HPLC, SDS-PAGE, and FACS. After radiolabelling with zirconium-89 (89Zr), radioconjugates were assessed for radiochemical purity, immunoreactivity, antigen binding affinity, and serum stability in vitro. [89Zr]Zr-Df-CI-8993 alone (1 mg/kg, 4.6 MBq) or in combination with 30 mg/kg unlabelled CI-8993, as well as isotype control [89Zr]Zr-Df-IgG1 (1 mg/kg, 4.6 MBq) were assessed in human VISTA knock-in female (C57BL/6 N-Vsirtm1.1(VSIR)Geno, huVISTA KI) or control C57BL/6 mice bearing syngeneic MB49 bladder cancer tumours; and in BALB/cnu /nu mice bearing pancreatic Capan-2 tumours.Stable constructs with an average chelator-to-antibody ratio of 1.81 were achieved. SDS-PAGE and SE-HPLC showed integrity of CI-8993 was maintained after conjugation; and ELISA indicated no impact of conjugation and radiolabelling on binding to human VISTA. PET imaging and biodistribution in MB49 tumour-bearing huVISTA KI female mice showed specific localisation of [89Zr]Zr-Df-CI-8993 to VISTA in spleen and tumour tissues expressing human VISTA. Specific tumour uptake was also demonstrated in Capan-2 xenografted BALB/cnu /nu mice.We radiolabelled and validated [89Zr]Zr-Df-CI-8993 for specific binding to huVISTA in vivo. Our results demonstrate that 89Zr-labelled CI-8993 is now suitable for targeting and imaging VISTA expression in human trials.Conclusions: CI-8993 is a fully human IgG1κ monoclonal antibody (mAb) that binds specifically to immune checkpoint molecule VISTA (V-domain Ig suppressor of T-cell activation). Phase I safety has been established in patients with advanced cancer (NCT02671955). To determine the pharmacokinetics and biodistribution of CI-8993 in patients, we aimed to develop 89Zr-labelled CI-8993 and validate PET imaging and quantitation in preclinical models prior to a planned human bioimaging trial.CI-8993 and human isotype IgG1 control were conjugated to the metal ion chelatorp -isothiocyanatobenzyl-desferrioxamine (Df). Quality of conjugates were assessed by SE-HPLC, SDS-PAGE, and FACS. After radiolabelling with zirconium-89 (89Zr), radioconjugates were assessed for radiochemical purity, immunoreactivity, antigen binding affinity, and serum stability in vitro. [89Zr]Zr-Df-CI-8993 alone (1 mg/kg, 4.6 MBq) or in combination with 30 mg/kg unlabelled CI-8993, as well as isotype control [89Zr]Zr-Df-IgG1 (1 mg/kg, 4.6 MBq) were assessed in human VISTA knock-in female (C57BL/6 N-Vsirtm1.1(VSIR)Geno, huVISTA KI) or control C57BL/6 mice bearing syngeneic MB49 bladder cancer tumours; and in BALB/cnu /nu mice bearing pancreatic Capan-2 tumours.Stable constructs with an average chelator-to-antibody ratio of 1.81 were achieved. SDS-PAGE and SE-HPLC showed integrity of CI-8993 was maintained after conjugation; and ELISA indicated no impact of conjugation and radiolabelling on binding to human VISTA. PET imaging and biodistribution in MB49 tumour-bearing huVISTA KI female mice showed specific localisation of [89Zr]Zr-Df-CI-8993 to VISTA in spleen and tumour tissues expressing human VISTA. Specific tumour uptake was also demonstrated in Capan-2 xenografted BALB/cnu /nu mice.We radiolabelled and validated [89Zr]Zr-Df-CI-8993 for specific binding to huVISTA in vivo. Our results demonstrate that 89Zr-labelled CI-8993 is now suitable for targeting and imaging VISTA expression in human trials.Graphical Abstract: CI-8993 is a fully human IgG1κ monoclonal antibody (mAb) that binds specifically to immune checkpoint molecule VISTA (V-domain Ig suppressor of T-cell activation). Phase I safety has been established in patients with advanced cancer (NCT02671955). To determine the pharmacokinetics and biodistribution of CI-8993 in patients, we aimed to develop 89Zr-labelled CI-8993 and validate PET imaging and quantitation in preclinical models prior to a planned human bioimaging trial.CI-8993 and human isotype IgG1 control were conjugated to the metal ion chelatorp -isothiocyanatobenzyl-desferrioxamine (Df). Quality of conjugates were assessed by SE-HPLC, SDS-PAGE, and FACS. After radiolabelling with zirconium-89 (89Zr), radioconjugates were assessed for radiochemical purity, immunoreactivity, antigen binding affinity, and serum stability in vitro. [89Zr]Zr-Df-CI-8993 alone (1 mg/kg, 4.6 MBq) or in combination with 30 mg/kg unlabelled CI-8993, as well as isotype control [89Zr]Zr-Df-IgG1 (1 mg/kg, 4.6 MBq) were assessed in human VISTA knock-in female (C57BL/6 N-Vsirtm1.1(VSIR)Geno, huVISTA KI) or control C57BL/6 mice bearing syngeneic MB49 bladder cancer tumours; and in BALB/cnu /nu mice bearing pancreatic Capan-2 tumours.Stable constructs with an average chelator-to-antibody ratio of 1.81 were achieved. SDS-PAGE and SE-HPLC showed integrity of CI-8993 was maintained after conjugation; and ELISA indicated no impact of conjugation and radiolabelling on binding to human VISTA. PET imaging and biodistribution in MB49 tumour-bearing huVISTA KI female mice showed specific localisation of [89Zr]Zr-Df-CI-8993 to VISTA in spleen and tumour tissues expressing human VISTA. Specific tumour uptake was also demonstrated in Capan-2 xenografted BALB/cnu /nu mice.We radiolabelled and validated [89Zr]Zr-Df-CI-8993 for specific binding to huVISTA in vivo. Our results demonstrate that 89Zr-labelled CI-8993 is now suitable for targeting and imaging VISTA expression in human trials. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
261. Evaluating [225Ac]Ac-FAPI-46 for the treatment of soft-tissue sarcoma in mice.
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Taddio, Marco F., Doshi, Suraj, Masri, Marwan, Jeanjean, Pauline, Hikmat, Firas, Gerlach, Alana, Nyiranshuti, Lea, Rosser, Ethan W., Schaue, Dorthe, Besserer-Offroy, Elie, Carlucci, Giuseppe, Radu, Caius G., Czernin, Johannes, Lückerath, Katharina, and Mona, Christine E.
- Subjects
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CANCER treatment , *IMMUNE checkpoint proteins , *TUMOR growth , *MICE , *PATIENT selection , *IMMUNOGLOBULINS - Abstract
Purpose: Fibroblast Activation Protein (FAP) is an emerging theranostic target that is highly expressed on cancer-associated fibroblasts and on certain tumor cells including sarcoma. We investigated the anti-tumor efficacy of [225Ac]Ac-FAPI-46 as monotherapy or in combination with immune checkpoint blockade (ICB) in immunocompetent murine models of sarcoma sensitive or resistant to ICB.[68Ga]Ga- and [225Ac]Ac-FAPI-46 were tested in subcutaneous FAP+ FSA fibrosarcoma bearing C3H/Sed/Kam mice. The efficacy of up to three cycles of 60 kBq [225Ac]Ac-FAPI-46 was evaluated as monotherapy and in combination with an anti-PD-1 antibody. Efficacy of [225Ac]Ac-FAPI-46 and/or ICB was further compared in FAP-overexpressing FSA (FSA-F) tumors that were sensitive to ICB or rendered ICB-resistant by tumor-induction in the presence of Abatacept.[225Ac]Ac-FAPI-46 was well tolerated up to 3 × 60 kBq but had minimal effect on FSA tumor growth. The combination of three cycles [225Ac]Ac-FAPI-46 and ICB resulted in growth delay in 55% of mice (6/11) and partial tumor regression in 18% (2/11) of mice. In FSA-F tumors with FAP overexpression, both [225Ac]Ac-FAPI-46 and ICB were effective without additional benefits from the combination. In locally immunosuppressed and ICB resistant FAP-F tumors, however, [225Ac]Ac-FAPI-46 restored responsiveness to ICB, resulting in significant tumor regression and tumor-free survival of 56% of mice in the combination group up to 60 days post treatment.[225Ac]Ac-FAPI-46 efficacy is correlated with tumoral FAP expression levels and can restore responsiveness to PD-1 ICB. These data illustrate that careful patient selection based on target expression and rationally designed combination therapies are critically important to maximize the therapeutic impact of FAP-targeting radioligands.Methods: Fibroblast Activation Protein (FAP) is an emerging theranostic target that is highly expressed on cancer-associated fibroblasts and on certain tumor cells including sarcoma. We investigated the anti-tumor efficacy of [225Ac]Ac-FAPI-46 as monotherapy or in combination with immune checkpoint blockade (ICB) in immunocompetent murine models of sarcoma sensitive or resistant to ICB.[68Ga]Ga- and [225Ac]Ac-FAPI-46 were tested in subcutaneous FAP+ FSA fibrosarcoma bearing C3H/Sed/Kam mice. The efficacy of up to three cycles of 60 kBq [225Ac]Ac-FAPI-46 was evaluated as monotherapy and in combination with an anti-PD-1 antibody. Efficacy of [225Ac]Ac-FAPI-46 and/or ICB was further compared in FAP-overexpressing FSA (FSA-F) tumors that were sensitive to ICB or rendered ICB-resistant by tumor-induction in the presence of Abatacept.[225Ac]Ac-FAPI-46 was well tolerated up to 3 × 60 kBq but had minimal effect on FSA tumor growth. The combination of three cycles [225Ac]Ac-FAPI-46 and ICB resulted in growth delay in 55% of mice (6/11) and partial tumor regression in 18% (2/11) of mice. In FSA-F tumors with FAP overexpression, both [225Ac]Ac-FAPI-46 and ICB were effective without additional benefits from the combination. In locally immunosuppressed and ICB resistant FAP-F tumors, however, [225Ac]Ac-FAPI-46 restored responsiveness to ICB, resulting in significant tumor regression and tumor-free survival of 56% of mice in the combination group up to 60 days post treatment.[225Ac]Ac-FAPI-46 efficacy is correlated with tumoral FAP expression levels and can restore responsiveness to PD-1 ICB. These data illustrate that careful patient selection based on target expression and rationally designed combination therapies are critically important to maximize the therapeutic impact of FAP-targeting radioligands.Results: Fibroblast Activation Protein (FAP) is an emerging theranostic target that is highly expressed on cancer-associated fibroblasts and on certain tumor cells including sarcoma. We investigated the anti-tumor efficacy of [225Ac]Ac-FAPI-46 as monotherapy or in combination with immune checkpoint blockade (ICB) in immunocompetent murine models of sarcoma sensitive or resistant to ICB.[68Ga]Ga- and [225Ac]Ac-FAPI-46 were tested in subcutaneous FAP+ FSA fibrosarcoma bearing C3H/Sed/Kam mice. The efficacy of up to three cycles of 60 kBq [225Ac]Ac-FAPI-46 was evaluated as monotherapy and in combination with an anti-PD-1 antibody. Efficacy of [225Ac]Ac-FAPI-46 and/or ICB was further compared in FAP-overexpressing FSA (FSA-F) tumors that were sensitive to ICB or rendered ICB-resistant by tumor-induction in the presence of Abatacept.[225Ac]Ac-FAPI-46 was well tolerated up to 3 × 60 kBq but had minimal effect on FSA tumor growth. The combination of three cycles [225Ac]Ac-FAPI-46 and ICB resulted in growth delay in 55% of mice (6/11) and partial tumor regression in 18% (2/11) of mice. In FSA-F tumors with FAP overexpression, both [225Ac]Ac-FAPI-46 and ICB were effective without additional benefits from the combination. In locally immunosuppressed and ICB resistant FAP-F tumors, however, [225Ac]Ac-FAPI-46 restored responsiveness to ICB, resulting in significant tumor regression and tumor-free survival of 56% of mice in the combination group up to 60 days post treatment.[225Ac]Ac-FAPI-46 efficacy is correlated with tumoral FAP expression levels and can restore responsiveness to PD-1 ICB. These data illustrate that careful patient selection based on target expression and rationally designed combination therapies are critically important to maximize the therapeutic impact of FAP-targeting radioligands.Conclusion: Fibroblast Activation Protein (FAP) is an emerging theranostic target that is highly expressed on cancer-associated fibroblasts and on certain tumor cells including sarcoma. We investigated the anti-tumor efficacy of [225Ac]Ac-FAPI-46 as monotherapy or in combination with immune checkpoint blockade (ICB) in immunocompetent murine models of sarcoma sensitive or resistant to ICB.[68Ga]Ga- and [225Ac]Ac-FAPI-46 were tested in subcutaneous FAP+ FSA fibrosarcoma bearing C3H/Sed/Kam mice. The efficacy of up to three cycles of 60 kBq [225Ac]Ac-FAPI-46 was evaluated as monotherapy and in combination with an anti-PD-1 antibody. Efficacy of [225Ac]Ac-FAPI-46 and/or ICB was further compared in FAP-overexpressing FSA (FSA-F) tumors that were sensitive to ICB or rendered ICB-resistant by tumor-induction in the presence of Abatacept.[225Ac]Ac-FAPI-46 was well tolerated up to 3 × 60 kBq but had minimal effect on FSA tumor growth. The combination of three cycles [225Ac]Ac-FAPI-46 and ICB resulted in growth delay in 55% of mice (6/11) and partial tumor regression in 18% (2/11) of mice. In FSA-F tumors with FAP overexpression, both [225Ac]Ac-FAPI-46 and ICB were effective without additional benefits from the combination. In locally immunosuppressed and ICB resistant FAP-F tumors, however, [225Ac]Ac-FAPI-46 restored responsiveness to ICB, resulting in significant tumor regression and tumor-free survival of 56% of mice in the combination group up to 60 days post treatment.[225Ac]Ac-FAPI-46 efficacy is correlated with tumoral FAP expression levels and can restore responsiveness to PD-1 ICB. These data illustrate that careful patient selection based on target expression and rationally designed combination therapies are critically important to maximize the therapeutic impact of FAP-targeting radioligands. [ABSTRACT FROM AUTHOR]
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- 2024
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262. A chitosan-camouflaged nanomedicine triggered by hierarchically stimuli to release drug for multimodal imaging-guided chemotherapy of breast cancer.
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Wang, Pei, Peng, Zhi, Zhang, Yanyan, Zhang, Xuejing, Chen, Xia, Li, Fan, Chen, Bo, Niu, Shiwei, Du, Kaili, and Zhu, Li-Min
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CANCER chemotherapy , *CHITOSAN , *BREAST cancer , *PACLITAXEL , *NANOMEDICINE , *COMPUTED tomography , *DRUGS , *INFRARED radiometry - Abstract
Breast cancer remains one of the most intractable diseases, especially the malignant form of metastasis, with which the cancer cells are hard to track and eliminate. Herein, the common known carbohydrate polymer chitosan (CS) was innovatively used as a shelter for the potent tumor-killing agent. The designed nanoparticles (NPs) not only enhance the solubility of hydrophobic paclitaxel (PTX), but also provide a "hide" effect for cytotoxic PTX in physiological condition. Moreover, coupled with the photothermal (PTT) properties of MoS 2 , results in a potent chemo/PTT platform. The MoS 2 @PTX-CS-K237 NPs have a uniform size (135 ± 17 nm), potent photothermal properties (η = 31.5 %), and environment-responsive (low pH, hypoxia) and near infrared (NIR) laser irradiation-triggered PTX release. Through a series of in vitro and in vivo experiments, the MoS 2 @PTX-CS-K237 showed high affinity and specificity for breast cancer cells, impressive tumor killing capacity, as well as the effective inhibitory effect of metastasis. Benefit from the unique optical properties of MoS 2 , this multifunctional nanomedicine also exhibited favorable thermal/PA/CT multimodality imaging effect on tumor-bearing mice. The system developed in this work represents the advanced design concept of hierarchical stimulus responsive drug release, and merits further investigation as a potential nanotheranostic platform for clinical translation. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2024
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263. Recent advances and strategies for nanocarrier-mediated topical therapy and theranostic for posterior eye disease.
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Faria, Maria João, González-Méijome, José M., Real Oliveira, M. Elisabete C.D., Carracedo, Gonzalo, and Lúcio, Marlene
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TARGETED drug delivery , *EYE diseases , *POSTERIOR segment (Eye) , *MACULAR degeneration , *RETINAL diseases , *DIABETIC retinopathy , *RETINAL blood vessels - Abstract
Nanocarrier-mediated topical therapies and theranostic are valuable strategies for targeting posterior ocular tissues. This review exalts safe-by-design approaches in the development of tuneable nanocarriers able to surpass the main ocular barriers. [Display omitted] Posterior eye disorders, such as age-related macular degeneration, diabetic retinopathy, and glaucoma, have a significant impact on human quality of life and are the primary cause of age-related retinal diseases among adults. There is a pressing need for innovative topical approaches to treat posterior eye disorders, as current methods often rely on invasive procedures with inherent risks. Limited success was attained in the realm of topical ophthalmic delivery through non-invasive means. Additionally, there exists a dearth of literature that delves into the potential of this approach for drug delivery and theranostic purposes, or that offers comprehensive design strategies for nanocarrier developers to surmount the significant physiological ocular barriers. This review offers a thorough and up-to-date state-of-the-art overview of 40 studies on therapeutic loaded nanocarriers and theranostic devices that, to the best of our knowledge, represent all successful works that reached posterior eye segments through a topical non-invasive administration. Most importantly, based on the successful literature studies, this review provides a comprehensive summary of the potential design strategies that can be implemented during nanocarrier development to overcome each ocular barrier. [ABSTRACT FROM AUTHOR]
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- 2024
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264. Bacterial lipase-responsive polydopamine nanoparticles for detection and synergistic therapy of wound biofilms infection.
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Jiang, Hezhong, Huang, Xiting, Li, Huanhuan, Ren, Feifei, Li, Dongqiu, Liu, Yuan, Tong, Yan, and Ran, Pan
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WOUND infections , *SOFT tissue infections , *LIPASES , *NANOPARTICLES , *CHRONIC wounds & injuries , *RHODAMINE B , *DOPAMINE receptors , *RUBIDIUM - Abstract
Wound biofilms represent an elusive conundrum in contemporary treatment and diagnostic options, accredited to their escalating antibiotic resistance and interference in chronic wound healing processes. Here, we developed mesoporous polydopamine (mPDA) nanoparticles, and grafted with rhodamine B (Rb) as biofilm lipase responsive detection probe, followed by π − π stacking mediated ciprofloxacin (CIP) loading to create mP-Rb@CIP nanoparticles. mPDA NPs with a melanin structure could quench fluorescence emissions of Rb. Once encountering biofilm in vivo , the ester bond in Rb and mPDA is hydrolyzed by elevated lipase concentrations, triggering the liberation of Rb and restore fluorescence emissions to achieve real-time imaging of biofilm-infected wounds. Afterwards, the 808 nm near-infrared (NIR) illumination initiates a spatiotemporal controlled antibacterial photothermal therapy (PTT), boosting its effectiveness through photothermal-triggered CIP release for synergistic biofilm eradication. The mP-Rb@CIP platform exhibits dual diagnostic and therapeutic functions, efficaciously treating biofilm-infected wounds in vivo and in vitro. Particularly, the mP-Rb@CIP/NIR procedure expedites wound-healing by alleviating oxidative stress, modulating inflammatory mediators, boosting collagen synthesis, and promoting angiogenesis. Taken together, the theranostic nanosystem strategy holds significant potential for addressing wound biofilm-associated infections. [Display omitted] • Over 30% of skin and soft tissue biofilm infections become chronic even after appropriate antibacterial treatment, accredited to their escalating antibiotic resistance and interference in chronic wound healing processes. • Challenges remain in the development of theranostic strategy having the capability of point-of-care diagnosis, life-cycle monitoring and on-demand elimination of biofilm infection. • Herein, a multifunctional theranostic nanoplatform has been fabricated to facilitate real-time detection of wound infection and photothermal-triggered ciprofloxacin release for biofilm eradication. • Bacterial infection-activated color changes of nanoparticals achieve real-time diagnosis of biofilm infection. • Afterwords, the 808 nm near-infrared illumination initiates a spatiotemporal controlled antibacterial photothermal therapy, boosting its effectiveness through photothermal-triggered drug release for synergistic biofilm eradication. • The designed platform plays a "one-stone-two-birds" role for diagnosing and treating biofilm, holding significant potential for addressing wound biofilm-associated infections. [ABSTRACT FROM AUTHOR]
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- 2024
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265. NQO1-activated multifunctional theranostic probe for imaging-guided mitochondria-targeted photodynamic therapy and boosting immunogenic cell death.
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Cao, Chen, Li, Jiansen, Zhang, Xinlu, Zhang, Xu, Gong, Xiaoqun, and Wang, Sheng
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PHOTODYNAMIC therapy , *CELL death , *CANCER cells , *REACTIVE oxygen species , *T helper cells - Abstract
NAD(P)H: quinine oxidoreductase (NQO1) is overexpressed in many types of cancer cells, and have been used as a biomarker for cancer diagnosis and targeted therapy. The development of activatable theranostic agents is highly desirable for precise cancer diagnosis and therapy. Herein, a NQO1-activated near-infrared multifunctional theranostic probe I-HCy-Q is successfully developed for imaging guided photodynamic therapy. The NIR fluorescence (λ ex/em = 685/703 nm) and capacity of reactive oxygen species generation are sensitive controllable by the level of NQO1, the linear detection range of NQO1 and limit of detection are 0.05–1.5 μg/mL and 5.66 ng/mL, respectively. On the one hand, I-HCy-Q can monitor the activity of NQO1 and distinguish the NQO1 positive cancer cells; on the other hand, the capacity of mitochondria-targeted photodynamic therapy makes I-HCy-Q an effective inducer of apoptosis and immunogenic cell death. Attribute to its complementary advantages, I-HCy-Q holds potential for the imaging and treatment of tumors in complex organisms. [Display omitted] • A NQO1-activated near-infrared multifunctional theranostic probe I-HCy-Q was successfully developed for imaging guided PDT. • I-HCy-Q could monitor the activity of NQO1 and distinguish the NQO1 positive cancer cells. • I-HCy-Q could anchor mitochondria and act as an effective apoptosis and immunogenic cell death inducer. [ABSTRACT FROM AUTHOR]
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- 2024
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266. Fabrication and characterization smart gold-polymer nanostructure as promising theranostic agent for dual-imaging and chemo-photothermal therapy of cancer: An in vitro study.
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Azizi, Mehdi, Pakravan, Asrin, Valizadeh, Hadi, Rahbarghazi, Reza, Dianat-Moghadam, Hassan, Bani, Farhad, Kahroba, Houman, Salehi, Roya, and Mehrmohammadi, Mohammad
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CANCER treatment , *COMPUTED tomography , *CANCER cell growth , *PHOTOTHERMAL conversion , *IN vitro studies , *CHEMORECEPTORS - Abstract
[Display omitted] • Smart Gold-polymer nanostructure was developed for dual CT/fluorescence imaging and chemo-photothermal therapy of cancer. • Pol-CD@GNSs-MTX showed significantly higher cell uptake compared to the Pol-CD@GNSs without MTX (P value < 0.001). • Combination chemo-PTT of MDA-MB231 cells with Pol-CD@GNSs-MTX led to the cells cycle arrest at the subG1 phase. • Combination chemo-PTT of MDA-MB231 cells with Pol-CD@GNSs-MTX led to apoptotic cell death. • NIR irradiation of cells pre-treated with synthesized nanoparticles showed efficient heat production rate. In order to enhance the effectiveness of cancer therapy, it is essential to have highly sensitive imaging techniques that provide accurate results and the selection of appropriate therapeutic strategies. Despite recent advances in technologies associated with tumor imaging, the application of conventional single-mode imaging is the subject of debate. Herein, we strategically engineered a nanostructure (GNSs-MTX@CD-Pol) designed from a pH-responsive polymer (Pol), gold nanostar (GNSs), carbon dot (CD), and methotrexate (MTX) as a theranostic agent for simultaneously fluorescent (FI) and X-ray computed tomography (CT) imaging and combination Chemo-Photothermal Therapy in response to near-infrared (NIR) laser irradiation. GNSs-MTX@CD-Pol NPs possess excellent photothermal conversion efficiency and dual FI/CT imaging properties, which are attributed to the strong NIR absorption and high atomic number of gold elements. Moreover, it is demonstrated that GNSs-MTX@CD-Pol NPs are effectively responding to tumor acidity. With the PTT, the growth of cancer cells can be remarkably ablated in vitro. The results of the cell cycle, apoptosis, real-time PCR, and western blotting test on MDA-MB-231 cells revealed antitumor effect of GNSs-MTX@CD-Pol NPs caused by combination Chemo-Photothermal Therapy. Based on their high stability and excellent biocompatibility, GNSs-MTX@CD-Pol NPs have great potential for the treatment of various types of tumors. [ABSTRACT FROM AUTHOR]
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- 2024
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267. Nanostructured Lipid Carrier Co-Loaded with Docetaxel and Magnetic Nanoparticles: Physicochemical Characterization and In Vitro Evaluation
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Auni Hamimi Idris, Che Azurahanim Che Abdullah, Nor Azah Yusof, Azren Aida Asmawi, and Mohd Basyaruddin Abdul Rahman
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docetaxel ,lipid-based carrier ,nanostructured lipid carrier ,theranostic ,Pharmacy and materia medica ,RS1-441 - Abstract
Lung cancer is currently the most prevalent cause of cancer mortality due to late diagnosis and lack of curative therapies. Docetaxel (Dtx) is clinically proven as effective, but poor aqueous solubility and non-selective cytotoxicity limit its therapeutic efficacy. In this work, a nanostructured lipid carrier (NLC) loaded with iron oxide nanoparticles (IONP) and Dtx (Dtx-MNLC) was developed as a potential theranostic agent for lung cancer treatment. The amount of IONP and Dtx loaded into the Dtx-MNLC was quantified using Inductively Coupled Plasma Optical Emission Spectroscopy and high-performance liquid chromatography. Dtx-MNLC was then subjected to an assessment of physicochemical characteristics, in vitro drug release, and cytotoxicity. Dtx loading percentage was determined at 3.98% w/w, and 0.36 mg/mL IONP was loaded into the Dtx-MNLC. The formulation showed a biphasic drug release in a simulated cancer cell microenvironment, where 40% of Dtx was released for the first 6 h, and 80% cumulative release was achieved after 48 h. Dtx-MNLC exhibited higher cytotoxicity to A549 cells than MRC5 in a dose-dependent manner. Furthermore, the toxicity of Dtx-MNLC to MRC5 was lower than the commercial formulation. In conclusion, Dtx-MNLC shows the efficacy to inhibit lung cancer cell growth, yet it reduced toxicity on healthy lung cells and is potentially capable as a theranostic agent for lung cancer treatment.
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- 2023
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268. TIGIT in Lung Cancer: Potential Theranostic Implications
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Carlo Pescia, Giuditta Pini, Edoardo Olmeda, Stefano Ferrero, and Gianluca Lopez
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TIGIT ,PD-L1 ,PD-1 ,prognostic ,predictive ,theranostic ,Science - Abstract
TIGIT (T cell immunoreceptor with Ig and ITIM domains) is a co-inhibitory receptor expressed on various immune cells, including T cells, NK cells, and dendritic cells. TIGIT interacts with different ligands, such as CD155 and CD112, which are highly expressed on cancer cells, leading to the suppression of immune responses. Recent studies have highlighted the importance of TIGIT in regulating immune cell function in the tumor microenvironment and its role as a potential therapeutic target, especially in the field of lung cancer. However, the role of TIGIT in cancer development and progression remains controversial, particularly regarding the relevance of its expression both in the tumor microenvironment and on tumor cells, with prognostic and predictive implications that remain to date essentially undisclosed. Here, we provide a review of the recent advances in TIGIT-blockade in lung cancer, and also insights on TIGIT relevance as an immunohistochemical biomarker and its possible theranostic implications.
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- 2023
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269. Magnetic Gels in Skin Cancer Treatment: A Review of Potential Applications in Diagnostics, Drug Delivery and Hyperthermia
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Marcos Luciano Bruschi and Glécilla Colombelli de Souza Nunes
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nanomedicine ,drug delivery systems ,magnetic gels ,hydrogels ,magnetic nanoparticles ,theranostic ,Pharmacy and materia medica ,RS1-441 - Abstract
Skin cancer (SC) is affecting an increasing number of people worldwide. Its lesions affect mainly the most exposed regions of the skin. SC is classified into to main categories: non-melanoma (basal cell carcinoma of the epidermis and squamous cell carcinoma) and melanoma (the abnormal proliferation of melanocytes, which is rarer, more hazardous, and more deadly). Prevention and early diagnosis are important actions, and surgery is often considered. After the removal of cancerous lesions, the local administration of medicine can guarantee anticancer therapeutic action, rapid healing and the recovery of tissue, ensuring the absence of recurrence. Magnetic gels (MGs) have attracted increased attention regarding their pharmaceutical and biomedical applications. They are magnetic nanoparticles (e.g., iron oxide nanoparticles) dispersed in a polymeric matrix, which constitute adaptive systems under a magnetic field. MGs can combine magnetic susceptibility, high elasticity, and softness, and are thus useful platforms for diagnostics, drug delivery, and also for hyperthermia. This manuscript reviews MGs as a technological strategy for the treatment of SC. An overview of SC and the treatment, types, and methods of preparing MGs are discussed. Moreover, the applications of MGs in SC and their future perspectives are considered. The combination of polymeric gels and magnetic nanoparticles continues to be investigated, and new products must hit the market. Clinical trials and new products are expected, due to the important advantages of MGs.
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- 2023
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270. Recent Advances in Green Metallic Nanoparticles for Enhanced Drug Delivery in Photodynamic Therapy: A Therapeutic Approach
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Alexander Chota, Blassan P. George, and Heidi Abrahamse
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cancer ,nanoparticles ,photosensitizer ,theranostic ,photodynamic therapy ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Globally, cancer is one of the leading causes of death among men and women, it is characterized by the unregulated proliferation of tumor cells. Some of the common risk factors associated with cancer development include the consistent exposure of body cells to carcinogenic agents such as alcohol, tobacco, toxins, gamma rays and alpha particles. Besides the above-mentioned risk factors, conventional therapies such as radiotherapy, and chemotherapy have also been linked to the development of cancer. Over the past decade, tremendous efforts have been invested in the synthesis of eco-friendly green metallic nanoparticles (NPs), and their medical application. Comparatively, metallic NPs have greater advantages over conventional therapies. Additionally, metallic NPs can be functionalized with different targeting moieties e.g., liposomes, antibodies, folic acid, transferrin, and carbohydrates. Herein, we review and discuss the synthesis, and therapeutic potential of green synthesized metallic NPs for enhanced cancer photodynamic therapy (PDT). Finally, the advantages of green hybridized activatable NPs over conventional photosensitizers (PSs) and the future perspectives of nanotechnology in cancer research are discussed in the review. Furthermore, we anticipate that the insights offered in this review will inspire the design and development of green nano-formulations for enhanced image-guided PDT in cancer treatment.
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- 2023
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271. Insights into Gold Nanoparticles Possibilities for Diagnosis and Treatment of the Head and Neck Upper Aerodigestive Tract Cancers
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Lídia M. Andrade and Guilherme M. J. Costa
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HNSCC ,nanomedicine ,gold nanoparticles ,theranostic ,image-guided surgery ,cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer affecting people and accounts for more than 300,000 deaths worldwide. Improvements in treatment modalities, including immunotherapy, have demonstrated promising prognoses for eligible patients. Nevertheless, the five-year overall survival rate has not increased significantly, and the tumor recurrence ratio remains at 50% or higher, except for patients with HPV-positive HNSCC. Over the last decades, nanotechnology has provided promising tools, especially for biomedical applications, due to some remarkable physicochemical properties of numerous nanomaterials, particularly gold nanoparticles. This review addresses the features and some applications of gold nanoparticles reported in the literature over the last five years regarding the diagnosis and treatment of head and neck cancer, highlighting the exciting possibilities of this nanomaterial in oncology. Methods: The scientific papers selected for this review were obtained from the PubMed Advanced, Web of Science, Scopus, ClinicalTrials.gov, and Google Scholar platforms. Conclusions: Results from papers applying gold nanoparticles have suggested that their application is a feasible approach to diagnostics, prognostics, and the treatment of HNC. Moreover, phase I clinical trials suggest that gold nanoparticles are safe and can potentially become theranostic agents for humans.
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- 2023
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272. Naphth[1,2-d]imidazoles Bioactive from β-Lapachone: Fluorescent Probes and Cytotoxic Agents to Cancer Cells
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Victória Laysna dos Anjos Santos, Arlan de Assis Gonsalves, Délis Galvão Guimarães, Sidney Silva Simplicio, Helinando Pequeno de Oliveira, Lara Polyana Silva Ramos, Marcília Pinheiro da Costa, Fátima de Cássia Evangelista de Oliveira, Claudia Pessoa, and Cleônia Roberta Melo Araújo
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heterocycle ,anticancer ,fluorescent probe ,theranostic ,naphthoimidazole ,Organic chemistry ,QD241-441 - Abstract
Theranostics combines therapeutic and imaging diagnostic techniques that are extremely dependent on the action of imaging agent, transporter of therapeutic molecules, and specific target ligand, in which fluorescent probes can act as diagnostic agents. In particular, naphthoimidazoles are potential bioactive heterocycle compounds to be used in several biomedical applications. With this aim, a group of seven naphth[1,2-d]imidazole compounds were synthesized from β-lapachone. Their optical properties and their cytotoxic activity against cancer cells and their compounds were evaluated and confirmed promising values for molar absorptivity coefficients (on the order of 103 to 104), intense fluorescence emissions in the blue region, and large Stokes shifts (20–103 nm). Furthermore, the probes were also selective for analyzed cancer cells (leukemic cells (HL-60). The naphth[1,2-d]imidazoles showed IC50 between 8.71 and 29.92 μM against HL-60 cells. For HCT-116 cells, values for IC50 between 21.12 and 62.11 μM were observed. The selective cytotoxicity towards cancer cells and the fluorescence of the synthesized naphth[1,2-d]imidazoles are promising responses that make possible the application of these components in antitumor theranostic systems.
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- 2023
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273. Shedding Lights on the Extracellular Vesicles as Functional Mediator and Therapeutic Decoy for COVID-19
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Abhimanyu Thakur
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COVID-19 ,exosome ,extracellular vesicles ,theranostic ,therapeutics ,vaccine ,Science - Abstract
COVID-19 is an infectious disease caused by the novel coronavirus (SARS-CoV-2) that first appeared in late 2019 and has since spread across the world. It is characterized by symptoms such as fever, cough, and shortness of breath and can lead to death in severe cases. To help contain the virus, measures such as social distancing, handwashing, and other public health measures have been implemented. Vaccine and drug candidates, such as those developed by Pfizer/BioNTech, AstraZeneca, Moderna, Novavax, and Johnson & Johnson, have been developed and are being distributed worldwide. Clinical trials for drug treatments such as remdesivir, dexamethasone, and monoclonal antibodies are underway and have shown promising results. Recently, exosomes have gained attention as a possible mediator of the COVID-19 infection. Exosomes, small vesicles with a size of around 30–200 nm, released from cells, contain viral particles and other molecules that can activate the immune system and/or facilitate viral entry into target cells. Apparently, the role of exosomes in eliciting various immune responses and causing tissue injury in COVID-19 pathogenesis has been discussed. In addition, the potential of exosomes as theranostic and therapeutic agents for the treatment of COVID-19 has been elaborated.
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- 2023
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274. Recent Advances in Metal-Based NanoEnhancers for Particle Therapy
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Yao-Chen Chuang, Ping-Hsiu Wu, Yao-An Shen, Chia-Chun Kuo, Wei-Jun Wang, Yu-Chen Chen, Hsin-Lun Lee, and Jeng-Fong Chiou
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particle therapy ,proton therapy ,radiosensitization ,radioresistance ,nanomedicine ,theranostic ,Chemistry ,QD1-999 - Abstract
Radiotherapy is one of the most common therapeutic regimens for cancer treatment. Over the past decade, proton therapy (PT) has emerged as an advanced type of radiotherapy (RT) that uses proton beams instead of conventional photon RT. Both PT and carbon-ion beam therapy (CIBT) exhibit excellent therapeutic results because of the physical characteristics of the resulting Bragg peaks, which has been exploited for cancer treatment in medical centers worldwide. Although particle therapies show significant advantages to photon RT by minimizing the radiation damage to normal tissue after the tumors, they still cause damage to normal tissue before the tumor. Since the physical mechanisms are different from particle therapy and photon RT, efforts have been made to ameliorate these effects by combining nanomaterials and particle therapies to improve tumor targeting by concentrating the radiation effects. Metallic nanoparticles (MNPs) exhibit many unique properties, such as strong X-ray absorption cross-sections and catalytic activity, and they are considered nano-radioenhancers (NREs) for RT. In this review, we systematically summarize the putative mechanisms involved in NRE-induced radioenhancement in particle therapy and the experimental results in in vitro and in vivo models. We also discuss the potential of translating preclinical metal-based NP-enhanced particle therapy studies into clinical practice using examples of several metal-based NREs, such as SPION, Abraxane, AGuIX, and NBTXR3. Furthermore, the future challenges and development of NREs for PT are presented for clinical translation. Finally, we propose a roadmap to pursue future studies to strengthen the interplay of particle therapy and nanomedicine.
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- 2023
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275. New Insights into the Biological Response Triggered by Dextran-Coated Maghemite Nanoparticles in Pancreatic Cancer Cells and Their Potential for Theranostic Applications
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Mihaela Balas, Daniela Predoi, Carmen Burtea, and Anca Dinischiotu
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iron oxide nanoparticles ,PANC-1 cells ,nanotoxicity ,theranostic ,caspase-1 ,Hsp60 ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Iron oxide nanoparticles are one of the most promising tools for theranostic applications of pancreatic cancer due to their unique physicochemical and magnetic properties making them suitable for both diagnosis and therapy. Thus, our study aimed to characterize the properties of dextran-coated iron oxide nanoparticles (DIO-NPs) of maghemite (γ-Fe2O3) type synthesized by co-precipitation and to investigate their effects (low-dose versus high-dose) on pancreatic cancer cells focusing on NP cellular uptake, MR contrast, and toxicological profile. This paper also addressed the modulation of heat shock proteins (HSPs) and p53 protein expression as well as the potential of DIO-NPs for theranostic purposes. DIO-NPs were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), dynamic light scattering analyses (DLS), and zeta potential. Pancreatic cancer cells (PANC-1 cell line) were exposed to different doses of dextran-coated ɣ-Fe2O3 NPs (14, 28, 42, 56 μg/mL) for up to 72 h. The results revealed that DIO-NPs with a hydrodynamic diameter of 16.3 nm produce a significant negative contrast using a 7 T MRI scanner correlated with dose-dependent cellular iron uptake and toxicity levels. We showed that DIO-NPs are biocompatible up to a concentration of 28 μg/mL (low-dose), while exposure to a concentration of 56 μg/mL (high-dose) caused a reduction in PANC-1 cell viability to 50% after 72 h by inducing reactive oxygen species (ROS) production, reduced glutathione (GSH) depletion, lipid peroxidation, enhancement of caspase-1 activity, and LDH release. An alteration in Hsp70 and Hsp90 protein expression was also observed. At low doses, these findings provide evidence that DIO-NPs could act as safe platforms in drug delivery, as well as antitumoral and imaging agents for theranostic uses in pancreatic cancer.
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- 2023
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276. Engineering theranostic liposomes for image guided drug delivery as a novel nanomedicine for cancer therapy
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Gubbins, James and Kostarelos, Kostas
- Subjects
616.99 ,Theranostic ,Multispectral Optoacoustic Tomography ,Thermosensitive ,Doxorubicin ,Liposome ,Indocyanine Green - Abstract
Cancer mortality is progression-dependent thus its treatment relies on effective therapy and monitoring of responses. Nanoparticles have long been used to improve the therapeutic index of drugs by facilitating their transit to the target site at higher concentrations than free drugs, whilst protecting healthy tissues from an often potent and cytotoxic payload. Through the EPR (enhanced permeability and retention) effect, injected, PEGylated nanoparticles preferentially accumulate in tumour tissue deeming them eminently suitable for cancer intervention for delivery of both therapeutic and contrast agents The development of theranostic liposomal systems comprising both imaging and therapeutic capabilities exploits the facets of liposomes, and forms an elegant strategy to address major problems which hinder effective cancer therapy. Liposomes can be tailored to be thermosensitive in a low hyperthermic range of ~42°C, above physiological temperature but below that which can induce tissue damage. This allows the use of heating as an external triggering modality to induce targeted drug release. Throughout the course of this work, the photoacoustic contrast agent ICG was successfully incorporated into PEGylated doxorubicin-encapsulating liposomes, marrying two FDA approved entities. The project commenced with the development of the basic liposomal-DOX. Differing lipid compositions of varying fluidities were tested against those which have been previously established. These compositions carried a range of phase transition temperatures, above which the liposomes release the encapsulated DOX. This study concluded with the generation of a library of liposomes with differing release kinetics at 42°C in simulated physiological conditions. The second section of the project investigated the methodology behind the incorporation of ICG into the liposomal bilayers. The lipid composition used for the study was based on the DOXIL® formulation, due to its robust structure and establishment in the field of cancer therapy. The protocols used varied on the basis of chronology in regards to the liposome preparation protocol. The film insertion method incorporated the ICG in initial lipid film generation. The freeze fracture protocol introduced the ICG during lipid film hydration. The post insertion protocol introduced ICG in the final stages of DOX loading. The downsizing protocol was also varied between extrusion and sonication. Through varying of the protocols and downsizing methodology, it was possible to incorporate differing ICG concentrations and attain differing levels of structural stability. The most successful liposome was then tested for its imaging potential in vivo through a photoacoustic imaging modality namely multispectral optoacoustic tomography. This validated accumulation of the liposomes at the tumour site along with co-localisation of both drug and dye. The project culminated in the combination of the two studies, producing a thermosensitive theranostic ICG labelled liposomal doxorubicin system. The system showed improved blood stability than the current clinical systems, and demonstrated imaging potential through IVIS based fluorescence imaging. Through exploitation of the photothermal effects of ICG within a thermosensitive lipid vesicle, it was also possible to induce drug release through irradiation with a non-thermal near-infrared laser. This shows promise for future therapy, allowing simultaneous imaging, optimum release induction and monitoring response to therapy, in a cheap, effective and time-efficient manner.
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- 2016
277. Development, Therapeutic Evaluation and Theranostic Applications of Cubosomes on Cancers: An Updated Review.
- Author
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Almoshari, Yosif
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DRUG carriers , *DELAYED diagnosis , *CANCER-related mortality , *GENE expression , *CANCER treatment , *BIODEGRADABLE nanoparticles , *THERAPEUTICS , *POLYMERSOMES - Abstract
Cancer is a group of disorders characterized by aberrant gene function and alterations in gene expression patterns. In 2020, it was anticipated that 19 million new cancer cases would be diagnosed globally, with around 10 million cancer deaths. Late diagnosis and interventions are the leading causes of cancer-related mortality. In addition, the absence of comprehensive cancer therapy adds to the burden. Many lyotropic non-lamellar liquid-crystalline-nanoparticle-mediated formulations have been developed in the last few decades, with promising results in drug delivery, therapeutics, and diagnostics. Cubosomes are nano-structured liquid-crystalline particles made of specific amphiphilic lipids in particular proportions. Their ability to encapsulate lipophilic, hydrophilic, and amphiphilic molecules within their structure makes them one of a kind. They are biocompatible, versatile drug carriers that can deliver medications through various routes of administration. Many preclinical studies on the use of cubosomes in cancer treatment and theranostic applications have been conducted. However, before cubosomes may be employed in clinical practice, significant technical advances must be accomplished. This review summarizes the development of cubosomes and their multifunctional role in cancer treatment based on the most recent reports. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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278. Pre-Study on Radiolabeling of Colistin with Lutetium-177 to Develop Theranostic Infection Agent.
- Author
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KARPUZ, Merve, OZGENC, Emre, ATLIHAN-GUNDOGDU, Evren, and BURAK, Zeynep
- Subjects
- *
RADIOLABELING , *BACTERIAL cell walls , *COLISTIN , *HIGH performance liquid chromatography , *CHELATING agents , *SALINE solutions , *BURDEN of care - Abstract
Infection is one of the important burdens on the health care system, not only due to leading morbidity and mortality but also because of the development of antibiotic resistance. Although the infection can be diagnosed by imaging techniques, more effective agents including radiopharmaceuticals may be required to image deep-seated infections. Imaging also plays a critical role in the choosing of optimum treatment options and following treatment. Theranostic agents offer many advantages such as monitoring the biodistribution and targeting of therapeutic agents, as well as rapid diagnosis and treatment. Colistin, a cationic peptide, leads to bacterial death through interaction with lipopolysaccharides in the cell wall of bacteria. In our study, 177Lu as radionuclide part and colistimethate sodium (a prodrug of colistin, CMS) as pharmaceutic part were chosen to prepare a radiopharmaceutical for imaging and treatment of infections. 177Lu-CMS complex was formed under room condition, and radiolabeling efficiency was determined by paper and high-performance liquid chromatography. The effect of the filtration process on radiolabeling was evaluated among the labeling efficiencies of filtered and un-filtered complexes. The different incubation times (5, 30, and 60 min) effect on the radiolabeling process was also evaluated. Moreover, in vitro stability of 177Lu-CMS complex in saline solution was assessed during 7 days. According to the results, desired radiolabeling efficiency was not obtained under tested conditions and stability studies. Therefore, various modifications such as the addition of chelating agents or stabilizers in the radiolabeling procedure should be made to increase the radiolabeling stability. Further studies regarding radiolabeling are surely needed, and our studies are continuing. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
279. Powering bioanalytical applications in biomedicine with light-responsive Janus micro-/nanomotors.
- Author
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Liu, Conghui, Huang, Juejiao, Xu, Tailin, and Zhang, Xueji
- Subjects
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JANUS particles , *CLINICAL medicine , *NANOMOTORS - Abstract
Possessing both unique asymmetric structures and remote-controlled active movement, light-responsive Janus micro-/nanomotors offer the possibility of breaking through the limitations of traditional biomedicine, and have fascinated and inspired researchers. Despite many obstacles toward the clinical application, impressive progress of light-responsive Janus micro-/nanomotors for bioanalytical applications has been made over the past decades. In this review, we first briefly introduced several main light-driven Janus micro-/nanomotors, then focused on their typical bioanalytical applications such as biosensing, bioimaging, and theranostic. In the end, we summarized the remaining challenges of light-responsive Janus micro-/nanomotors in the practical application and also proposed potential solutions in the future. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
280. All-in-one theranostic nano-platform based on polymer nanoparticles for BRET/FRET-initiated bioluminescence imaging and synergistically anti-inflammatory therapy for ulcerative colitis.
- Author
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Yan, Xiangji, Yang, Chunhua, Yang, Mei, Ma, Yana, Zhang, Yuanyuan, Zhang, Yujie, Liu, Cui, Xu, Qiuran, Tu, Kangsheng, and Zhang, Mingzhen
- Subjects
- *
INFLAMMATORY bowel diseases , *ULCERATIVE colitis , *BIOLUMINESCENCE , *FLUORESCENCE resonance energy transfer , *BETULINIC acid , *POLYMERS - Abstract
Background: Ulcerative colitis (UC), a subtype of inflammatory bowel disease (IBD), has evolved into a global burden given its high incidence. There is a clinical need to create better diagnostic and therapeutic approaches to UC. Results: We fabricated P-selectin binding peptide-decorated poly lactic-co-glycolic acid (PBP-PLGA-NP) doped with two lipophilic dyes, DiL and DiD. Meanwhile, two low-toxic anti-inflammatory natural products (betulinic acid [BA] and resveratrol [Res]) were co-loaded in the PBP-PLGA-NP system. The BA/Res-loaded NPs had an average size of around 164.18 nm with a negative zeta potential (− 25.46 mV). Entrapment efficiencies of BA and Res were 74.54% and 52.33%, respectively, and presented a sustained drug release profile. Further, the resulting PBP-PLGA-NP could be internalized by RAW 264.7 cells and Colon-26 cells efficiently in vitro and preferentially localized to the inflamed colon. When intravenously injected with luminol, MPO-dependent bioluminescence imaging to visualize tissue inflammation was activated by the bioluminescence and fluorescence resonance energy transfer (BRET-FRET) effect. Importantly, injected NPs could remarkably alleviate UC symptoms yet maintain intestinal microbiota homeostasis without inducing organ injuries in the mice models of colitis. Conclusions: This theranostic nano-platform not only serves as a therapeutic system for UC but also as a non-invasive and highly-sensitive approach for accurately visualizing inflammation. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
281. Teranóstica: conceptos y aplicaciones.
- Author
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Jaimovich, Rodrigo
- Abstract
Copyright of Revista Médica Clínica Las Condes is the property of Editorial Sanchez y Barcelo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2022
- Full Text
- View/download PDF
282. Radiolabelled Peptides: Optimal Candidates for Theranostic Application in Oncology.
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Hall, Andrew J. and Haskali, Mohammad B.
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- *
INDIVIDUALIZED medicine , *PEPTIDES , *NUCLEAR medicine , *COMPANION diagnostics , *ONCOLOGY - Abstract
Theranostics are drugs suitable for use in both diagnostic and therapeutic applications, and have played an important role in the advancement of modern nuclear medicine. This review explains key elements that are common to successful theranostics and highlights significant developments in the field, including our own. Specific focus is given to peptides and those features that make them most suitable for theranostic application, as well as some key radioisotopes owing to their favourable properties and high clinical utility. This report provides an overview of the techniques at the researcher's disposal, how they have been applied to current clinically significant targets, and how they might be used and improved upon for future targets. Diagnosis and therapy using the same radioactive peptide (theranostics) is a paradigm-changing form of personalised medicine for cancer management with striking efficacy and low toxicity. The ability of theranostics to 'see what you treat' facilitates personalised patient management and allows rapid translation from bench to patient by enabling direct visualisation and quantification of the target. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
283. Nanofibers for Medical Diagnosis and Therapy
- Author
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Prabhu, Priyanka, Barhoum, Ahmed, editor, Bechelany, Mikhael, editor, and Makhlouf, Abdel Salam Hamdy, editor
- Published
- 2019
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284. Remotely Triggered Nanotheranostics
- Author
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Parchur, Abdul K., Jagtap, Jaidip M., Sharma, Gayatri, Gogineni, Venkateswara, White, Sarah B., Joshi, Amit, Vo-Dinh, Tuan, Series Editor, Rai, Prakash, editor, and Morris, Stephanie A., editor
- Published
- 2019
- Full Text
- View/download PDF
285. Perspectives for Characterizing Drug Component of Theranostic Products Containing Nanomaterials
- Author
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Sayes, Christie M., Hickey, Anthony J., Vo-Dinh, Tuan, Series Editor, Rai, Prakash, editor, and Morris, Stephanie A., editor
- Published
- 2019
- Full Text
- View/download PDF
286. Translational Nanodiagnostics for In Vivo Cancer Detection
- Author
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Liu, Christina H., Tandon, Pushpa, Russell, Luisa M., Vo-Dinh, Tuan, Series Editor, Rai, Prakash, editor, and Morris, Stephanie A., editor
- Published
- 2019
- Full Text
- View/download PDF
287. Theranostics: A Historical Perspective of Cancer Nanotechnology Paving the Way for Simultaneous Use Applications
- Author
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Hartshorn, Christopher M., Morris, Stephanie A., Vo-Dinh, Tuan, Series Editor, Rai, Prakash, editor, and Morris, Stephanie A., editor
- Published
- 2019
- Full Text
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288. Chitosan-Based Systems for Theranostic Applications
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Balan, V., Malihin, S., Verestiuc, Liliana, Jana, Sougata, editor, and Jana, Subrata, editor
- Published
- 2019
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289. Nucleic Acid Guided Molecular Tool for In-Vivo Theranostic Applications
- Author
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Baba, Shahnawaz Ahmad, Mutreja, Ruchi, Beniwal, Arun, Jain, Shubham, Yadav, Ekta, Ghosh, Tamoghna, Navani, Naveen K., Kumar, Piyush, Yadav, Gulab Singh, editor, Kumar, Vikas, editor, and Aggarwal, Neeraj K., editor
- Published
- 2019
- Full Text
- View/download PDF
290. Something old has become new: PET imaging of neural-crest tumors with [18F]-meta-fluorobenzylguanidine
- Author
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Filippi, Luca and Schillaci, Orazio
- Published
- 2023
- Full Text
- View/download PDF
291. Nanoparticle as a powerful tool to penetrate the Blood-brain barrier in the treatment of Neurodegenerative disease: Focus on recent advances
- Author
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Kalaiselvi, S., Manimaran, V., and Damodharan, N
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- 2020
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292. Cobalt magnetic nanoparticles as theranostics: Conceivable or forgettable?
- Author
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Petrarca Claudia, Poma Anna Maria, Vecchiotti Giulia, Bernardini Giovanni, Niu Qiao, Cattaneo Anna Giulia, Di Gioacchino Mario, and Sabbioni Enrico
- Subjects
cobalt ,magnetism ,nanoparticles ,safety ,synthesis ,theranostic ,toxicity ,Technology ,Chemical technology ,TP1-1185 ,Physical and theoretical chemistry ,QD450-801 - Published
- 2020
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293. Revisiting the potential of South American rattlesnake Crotalus durissus terrificus toxins as therapeutic, theranostic and/or biotechnological agents.
- Author
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Hayashi, Mirian A.F., Campeiro, Joana D., and Yonamine, Camila M.
- Subjects
- *
CROTALUS , *RATTLESNAKES , *VENOM , *TOXINS , *ANTI-inflammatory agents , *ANTIPARASITIC agents , *FIBRIN tissue adhesive , *DRUGS - Abstract
The potential biotechnological and biomedical applications of the animal venom components are widely recognized. Indeed, many components have been used either as drugs or as templates/prototypes for the development of innovative pharmaceutical drugs, among which many are still used for the treatment of human diseases. A specific South American rattlesnake, named Crotalus durissus terrificus, shows a venom composition relatively simpler compared to any viper or other snake species belonging to the Crotalus genus, although presenting a set of toxins with high potential for the treatment of several still unmet human therapeutic needs, as reviewed in this work. In addition to the main toxin named crotoxin, which is under clinical trials studies for antitumoral therapy and which has also anti-inflammatory and immunosuppressive activities, other toxins from the C. d. terrificus venom are also being studied, aiming for a wide variety of therapeutic applications, including as antinociceptive, anti-inflammatory, antimicrobial, antifungal, antitumoral or antiparasitic agent, or as modulator of animal metabolism, fibrin sealant (fibrin glue), gene carrier or theranostic agent. Among these rattlesnake toxins, the most relevant, considering the potential clinical applications, are crotamine, crotalphine and gyroxin. In this narrative revision, we propose to organize and present briefly the updates in the accumulated knowledge on potential therapeutic applications of toxins collectively found exclusively in the venom of this specific South American rattlesnake, with the objective of contributing to increase the chances of success in the discovery of drugs based on toxins. [Display omitted] • Biotechnological and biomedical applications of toxins are widely recognized. • Rattlesnake toxins have high potential for treating several human diseases. • Potential therapeutic applications of rattlesnake toxins were reviewed here. • Several rattlesnake toxins are under preclinical or clinical studies. • Some rattlesnake toxins share similar therapeutic application. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
294. HEDEFE YÖNELİK TEDAVİDE GÜNCEL YAKLAŞIMLAR: LUTESYUM-177 İLE İŞARETLİ RADYOFARMASÖTİKLER.
- Author
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HIŞIR, Dorukhan, EKİNCİ, Meliha, and İLEM-ÖZDEMİR, Derya
- Abstract
Copyright of Journal of Faculty of Pharmacy of Ankara University / Ankara Üniversitesi Eczacilik Fakültesi Dergisi is the property of Ankara University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2022
- Full Text
- View/download PDF
295. Radioactive nuclei for β+γ PET and theranostics: selected candidates.
- Author
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Matulewicz, Tomasz
- Subjects
- *
POSITRON emission tomography , *RADIOACTIVE tracers , *DIAGNOSTIC imaging , *PHOTOMULTIPLIERS , *NUCLEAR physics , *COMPANION diagnostics , *POSITRON emission - Abstract
Positron emission tomography (PET) is an established medical diagnostic imaging method. Continuous improvements are aimed at refining image reconstruction, reducing the amount of radioactive tracer and combining with targeted therapy. Time-of-flight (TOF)-PET provides the localization of the tracer through improved time resolution, nuclear physics may contribute to this goal via selection of radioactive nuclei emitting additional γ-rays. This additional radiation, when properly detected, localizes the decay of the tracer at the line of response (LoR) determined by two detected 511 keV quanta. Selected candidates are presented. Some are particularly interesting, as they are strong candidates for theranostic applications. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
296. Mesoporous silica coated gold nanorods: a multifunctional theranostic platform for radiotherapy and X-ray imaging.
- Author
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Koosha, Fereshteh, Farsangi, Zohreh Jomeh, Samadian, Hadi, and Amini, Seyed Mohammad
- Abstract
The development of theranostic nanostructures is one of the most advanced branches of pharmaceutical and medical sciences in the world today. Due to the unique properties such as surface plasmon resonance, Raman signal amplification, high atomic number, gold nanostructures are of particular interest to researchers. It has been shown that the formation of mesoporous silica coating with suitable thickness and microstructural properties can increase thermal stability and increase the possibility of loading anticancer drugs in theranostic formulations. In this study, gold nanorods were synthesized by seed-mediated growth method, and then by the sol-gel technique, nanorods were used as a template to create mesoporous silica coating. In the last step, PEG silane was used to create a polyethylene glycol coating at the surface of nanostructures. Based on HRTEM micrographs, the fabricated nanostructures had an average size of approximately 80 nm, and the nanoparticles entirely separated from each other. These nanostructures were non-toxic and could be well used as X-ray contrast agents. Only at high concentrations, these nanostructures were able to have a significant effect on radiotherapy with cobalt 60 source. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
297. Fibroblast-Activated Protein Inhibitor PET/CT: Cancer Diagnosis and Management.
- Author
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Kuyumcu, Serkan, Sanli, Yasemin, and Subramaniam, Rathan M.
- Subjects
CANCER diagnosis ,FIBROBLASTS ,RADIOACTIVE tracers ,TRANSLOCATOR proteins ,PROTEINS ,RADIOLABELING ,GIBBERELLINS - Abstract
Fibroblast activation protein (FAP), overexpressed on cancer-associated fibroblasts (CAFs), is a novel target for molecular imaging of various tumors. Recently, the development of several small-molecule FAP inhibitors for radiolabeling with
68 Ga has resulted in the emergence of studies evaluating its clinical role in cancer imaging. Preliminary findings have demonstrated that, in contrast to radiotracers taking advantage of cancer-specific targets such as PSMA and DOTATATE, FAPs as a target are the most promising that can compete with18 FDG in terms of widespread indications. They also have the potential to overcome the shortcomings of18 FDG, particularly false-positive uptake due to inflammatory or infectious processes, low sensitivity in certain cancer types, and radiotherapy planning. In addition, the attractive theranostic properties may facilitate the treatment of many refractory cancers. This review summarizes the current FAP variants and related clinical studies, focusing on radiopharmacy, dosimetry, and diagnostic and theranostic applications. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
298. Functional pre-therapeutic evaluation by genome editing of variants of uncertain significance of essential tumor suppressor genes.
- Author
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Billaud, Amandine, Chevalier, Louise-Marie, Augereau, Paule, Frenel, Jean-Sebastien, Passot, Christophe, Campone, Mario, and Morel, Alain
- Subjects
- *
GENOME editing , *TUMOR suppressor genes , *BRCA genes , *POLY(ADP-ribose) polymerase - Abstract
Background: Targeted therapies in oncology are promising but variants of uncertain significance (VUS) limit their use for clinical management and necessitate functional testing in vitro. Using BRCA1 and BRCA2 variants, which have consequences on PARP inhibitor sensitivity, and POLE variants, potential biomarkers of immunotherapy response, we developed a rapid functional assay based on CRISPR-Cas9 genome editing to determine the functional consequences of these variants having potentially direct implications on patients' access to targeted therapies. Methods: We first evaluated the functional impact of 26 BRCA1 and 7 BRCA2 variants by editing and comparing NGS results between the variant of interest and a silent control variant. Ten of these variants had already been classified as benign or pathogenic and were used as controls. Finally, we extended this method to the characterization of POLE VUS. Results: For the 23 variants that were unclassified or for which conflicting interpretations had been reported, 15 were classified as functionally normal and 6 as functionally abnormal. Another two variants were found to have intermediate consequences, both with potential impacts on splicing. We then compared these scores to the patients' responses to PARP inhibitors when possible. Finally, to prove the application of our method to the classification of variants from other tumor suppressor genes, we exemplified with three POLE VUS. Among them, two were classified with an intermediate functional impact and one was functionally abnormal. Eventually, four POLE variants previously classified in databases were also evaluated. However, we found evidence of a discordance with the classification, variant p.Leu424Val being found here functionally normal. Conclusions: Our new rapid functional assay can be used to characterize the functional implication of BRCA1 and BRCA2 variants, giving patients whose variants were evaluated as functionally abnormal access to PARP inhibitor treatment. Retrospective analysis of patients' responses to PARP inhibitors, where accessible, was consistent with our functional score evaluation and confirmed the accuracy of our protocol. This method could potentially be extended to the classification of VUS from all essential tumor suppressor genes and can be performed within a timeframe compatible with clinical applications, thereby having a direct theranostic impact. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
299. A non-internalised CD38-binding radiolabelled single-domain antibody fragment to monitor and treat multiple myeloma.
- Author
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Duray, Elodie, Lejeune, Margaux, Baron, Frederic, Beguin, Yves, Devoogdt, Nick, Krasniqi, Ahmet, Lauwers, Yoline, Zhao, Yong Juan, D'Huyvetter, Matthias, Dumoulin, Mireille, and Caers, Jo
- Subjects
- *
MULTIPLE myeloma , *SINGLE-photon emission computed tomography , *BORTEZOMIB , *PLASMA cell diseases , *CANCER cells , *DARATUMUMAB - Abstract
Background: Antibody-based therapies targeting CD38 are currently used as single agents as well as in combination regimens for multiple myeloma, a malignant plasma cell disorder. In this study, we aimed to develop anti-CD38 single-domain antibodies (sdAbs) that can be used to trace CD38+ tumour cells and subsequently used for targeted radionuclide therapy. SdAbs are derived from Camelidae heavy-chain antibodies and have emerged as promising theranostic agents due to their favourable pharmacological properties. Methods: Four different anti-CD38 sdAbs were produced, and their binding affinities and potential competition with the monoclonal antibody daratumumab were tested using biolayer interferometry. Their binding kinetics and potential cell internalisation were further studied after radiolabelling with the diagnostic radioisotope Indium-111. The resulting radiotracers were evaluated in vivo for their tumour-targeting potential and biodistribution through single-photon emission computed tomography (SPECT/CT) imaging and serial dissections. Finally, therapeutic efficacy of a lead anti-CD38 sdAb, radiolabelled with the therapeutic radioisotope Lutetium-177, was evaluated in a CD38+ MM xenograft model. Results : We retained anti-CD38 sdAb #2F8 as lead based on its excellent affinity and superior stability, the absence of competition with daratumumab and the lack of receptor-mediated internalisation. When intravenously administered to tumour-xenografted mice, radiolabelled sdAb #2F8 revealed specific and sustained tumour retention with low accumulation in other tissues, except kidneys, resulting in high tumour-to-normal tissue ratios. In a therapeutic setting, myeloma-bearing mice received three consecutive intravenous administrations of a high (18.5 MBq) or a low radioactive dose (9.3 MBq) of 177Lu-DTPA-2F8 or an equal volume of vehicle solution. A dose-dependent tumour regression was observed, which translated into a prolonged median survival from 43 days for vehicle-treated mice, to 62 days (p = 0.027) in mice receiving the low and 65 days in mice receiving the high (p = 0.0007) radioactive dose regimen, respectively. Conclusions: These results highlight the theranostic potential of radiolabelled anti-CD38 sdAbs for the monitoring and treatment of multiple myeloma. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
300. Sequential enzyme-activated macrotheranostic probe for selective tumor mitochondria targeting.
- Author
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Ma, Di, Zong, Qingyu, Du, Yuchen, Yu, Fangzhou, Xiao, Xuan, Sun, Rong, Guo, Yuan, Wei, Xinhua, and Yuan, Youyong
- Subjects
MITOCHONDRIA ,CANCER cells ,ENZYME activation ,DNA probes ,REACTIVE oxygen species ,MITOCHONDRIAL membranes ,MEMBRANE potential - Abstract
Subcellular organelle targeted imaging and therapy are of enormous interest in cancer theranostics. However, the lack of tumor-selective organelle targeting has compromised their efficacy and safety. In this work, we found that the near-infrared (NIR) fluorophore hemicyanine (CyNH 2) can selectively target mitochondria with strong cytotoxicity through decreasing the mitochondrial membrane potential and increasing the intracellular reactive oxygen species (ROS) levels. A macrotheranostic probe (denoted as PLCy) based on conjugating CyNH 2 with an acetylated lysine group was developed with masked fluorescence and cytotoxicity, which could both be unmasked through sequential activation by cancer cells overexpressing histone deacetylases (HDACs) and cathepsin L (CTSL) enzymes for selective cancer cell mitochondria-targeted imaging and therapy. In vitro and in vivo studies confirmed that the specific fluorescence turn-on and toxicity were restored in cancer cells and efficiently inhibited tumor growth. This macrotheranostic probe with sequential enzyme activation and mitochondrial targeting is expected to have promising applications in imaging-guided cancer therapy with high specificity and efficiency. To improve the targeting efficiency and enhance the anti-cancer activities of macrotheranostic probe. We designed macrotheranostic probe PLCy that can be activated via sequential enzymes for selective tumor mitochondria targeting. More importantly, the activated CyNH 2 can decrease the mitochondrial membrane potential and elevate the reactive oxygen species level in cancer cells without light irradiation, which can further induce apoptosis of tumor cells for chemotherapy. Therefore, the use of sequential enzyme activation and mitochondria targeting strategies in the context of enzymatic activation may provide a general strategy for organelle-targeted imaging and therapy with high specificity and efficiency. [Display omitted] [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
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