52 results on '"Deju Ye"'
Search Results
2. Recent Advances in Activatable Probes for Molecular Imaging by <scp>Stimuli‐Controlled</scp> Disassembly
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Weijing Huang, Yanling Yang, and Deju Ye
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General Chemistry - Published
- 2023
3. Controlled sequential in situ self-assembly and disassembly of a fluorogenic cisplatin prodrug for cancer theranostics
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Xidan Wen, Rui Zhang, Yuxuan Hu, Luyan Wu, He Bai, Dongfan Song, Yanfeng Wang, Ruibing An, Jianhui Weng, Shuren Zhang, Rong Wang, Ling Qiu, Jianguo Lin, Guandao Gao, Hong Liu, Zijian Guo, and Deju Ye
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Multidisciplinary ,General Physics and Astronomy ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology - Abstract
Temporal control of delivery and release of drugs in tumors are important in improving therapeutic outcomes to patients. Here, we report a sequential stimuli-triggered in situ self-assembly and disassembly strategy to direct delivery and release of theranostic drugs in vivo. Using cisplatin as a model anticancer drug, we design a stimuli-responsive small-molecule cisplatin prodrug (P-CyPt), which undergoes extracellular alkaline phosphatase-triggered in situ self-assembly and succeeding intracellular glutathione-triggered disassembly process, allowing to enhance accumulation and elicit burst release of cisplatin in tumor cells. Compared with cisplatin, P-CyPt greatly improves antitumor efficacy while mitigates off-target toxicity in mice with subcutaneous HeLa tumors and orthotopic HepG2 liver tumors after systemic administration. Moreover, P-CyPt also produces activated near-infrared fluorescence (at 710 nm) and dual photoacoustic imaging signals (at 700 and 750 nm), permitting high sensitivity and spatial-resolution delineation of tumor foci and real-time monitoring of drug delivery and release in vivo. This strategy leverages the advantages offered by in situ self-assembly with those of intracellular disassembly, which may act as a general platform for the design of prodrugs capable of improving drug delivery for cancer theranostics.
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- 2023
4. Plasmon-Accelerated Generation of Singlet Oxygen on an Au/MoS2 Nanohybrid for Enhanced Photodynamic Killing of Bacterial Pathogens/Cancerous Cells
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Muhammad Rizwan Younis, Ruibing An, Yang Wang, Gang He, Bhaskar Gurram, Shouju Wang, Jing Lin, Deju Ye, Peng Huang, and Xing-Hua Xia
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Biomaterials ,Biochemistry (medical) ,Biomedical Engineering ,General Chemistry - Published
- 2022
5. Smart Nanosensitizers for Activatable Sono‐Photodynamic Immunotherapy of Tumors by Redox‐Controlled Disassembly
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Lingjun Liu, Junya Zhang, Ruibing An, Qi Xue, Xi Cheng, Yuxuan Hu, Zheng Huang, Luyan Wu, Wenhui Zeng, Yinxing Miao, Jie Li, Yu Zhou, Hong‐Yuan Chen, Hong Liu, and Deju Ye
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General Medicine ,General Chemistry ,Catalysis - Abstract
Tumor-targeted and stimuli-activatable nanosensitizers are highly desirable for cancer theranostics. However, design of smart nanosensitizers with multiple imaging signals and synergistic therapeutic activities switched on is challenging. Herein, we report tumor-targeted and redox-activatable nanosensitizers (1-NPs) for sono-photodynamic immunotherapy of tumors by molecular co-assembly and redox-controlled disassembly. 1-NPs show a high longitudinal relaxivity (r1 = 18.7 ± 0.3 mM-1 s-1), but "off" dual fluorescence (FL) emissions (at 547 and 672 nm), "off" sono-photodynamic therapy and indoleamine 2,3-dioxygenase 1 (IDO1) inhibition activities. Upon reduction by glutathione (GSH), 1-NPs rapidly disassemble and remotely release small molecules 2-Gd, Zn-PPA-SH and NLG919, concurrently switching on (1) dual FL emissions, (2) sono-photodynamic therapy and (3) IDO1 inhibition activities. After systemic injection, 1-NPs are effective for bimodal FL and magnetic resonance (MR) imaging-guided sono-photodynamic immunotherapy of orthotropic breast and brain tumors in mice under combined ultrasound (US) and 671-nm laser irradiation.
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- 2023
6. Alkaline Phosphatase Enabled Fluorogenic Reaction and in situ Coassembly of Near-Infrared and Radioactive Nanoparticles for in vivo Imaging
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Yuxuan Hu, Yinxing Miao, Junya Zhang, Yinfei Chen, Ling Qiu, Jianguo Lin, and Deju Ye
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Mechanical Engineering ,General Materials Science ,Bioengineering ,General Chemistry ,Condensed Matter Physics - Published
- 2021
7. Activatable Multimodal Probes for In Vivo Imaging and Theranostics
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Yuqi Wang, Yuxuan Hu, and Deju Ye
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Diagnostic Imaging ,Neoplasms ,Optical Imaging ,Humans ,General Chemistry ,General Medicine ,Precision Medicine ,Catalysis ,Fluorescent Dyes ,Molecular Imaging - Abstract
Multimodal imaging, which harnesses two or more imaging modalities to produce complementary anatomical and molecular information of a living subject, has become as a powerful tool in both basic biomedical research and clinical diagnosis. The progresses in multimodal imaging are paralleled by the advances in multimodal probes, particularly activatable multimodal imaging probes that can generate concurrent switches in different imaging modality signals upon interaction with a molecular target. These probes are extremely promising for in vivo imaging. In this Minireview, we summarize the recent progress in activatable multimodal probes for in vivo imaging and cancer theranostics, focusing on their design principle, signal activation mechanism and biomedical applications. The current challenges and perspectives for future developments of activatable multimodal probes are also briefly discussed. We hope that this Minireview will provide inspiration for the design of other activatable multimodal probes for improving in vivo imaging and theranostics.
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- 2022
8. Near‐Infrared Electrochromic Behavior of Dibenzothiepin Derivatives Attached with Two Michler's Hydrol Blue Units
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Yusuke Ishigaki, Masaki Takata, Takuya Shimajiri, Luyan Wu, Wenhui Zeng, Deju Ye, and Takanori Suzuki
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Organic Chemistry ,General Chemistry ,Catalysis - Abstract
10,11-Bis[bis(4-dimethylaminophenyl)methylene]dibenzo[bf]thiepin (1) and -oxepin (2) were prepared as stable yellow crystalline compounds, which are the cyclic analogues of electron-donating hexaarylbutadienes. Upon two-electron oxidation, they are reversibly transformed into the title dications (1
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- 2022
9. A Ratiometric Photoacoustic Probe with a Reversible Response to Hydrogen Sulfide and Hydroxyl Radicals for Dynamic Imaging of Liver Inflammation
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Luyan Wu, Wenhui Zeng, Yusuke Ishigaki, Junya Zhang, He Bai, Takashi Harimoto, Takanori Suzuki, and Deju Ye
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Photoacoustic Techniques ,Mice ,Liver ,Hydroxyl Radical ,Spectrum Analysis ,Animals ,General Medicine ,Hydrogen Sulfide ,General Chemistry ,Oxidation-Reduction ,Catalysis ,Fluorescent Dyes - Abstract
Reversible imaging probes that allow for the dynamic visualization of the redox cycle between hydroxyl radical (⋅OH) and hydrogen sulfide (H
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- 2022
10. Enzyme‐Mediated In Situ Self‐Assembly Promotes In Vivo Bioorthogonal Reaction for Pretargeted Multimodality Imaging
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Hong-Yuan Chen, Jianguo Lin, Ling Qiu, Deju Ye, Kai Guo, Yidan Sun, Junya Zhang, Jian Wang, Xidan Wen, Yuxuan Hu, Yinxing Miao, and Yinfei Chen
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Gallium Radioisotopes ,Multimodal Imaging ,Catalysis ,Small Molecule Libraries ,Tetrazine ,chemistry.chemical_compound ,Cyclooctanes ,Mice ,In vivo ,medicine ,Animals ,Humans ,Particle Size ,Pretargeting ,medicine.diagnostic_test ,Molecular Structure ,Magnetic resonance imaging ,General Chemistry ,Neoplasms, Experimental ,General Medicine ,Alkaline Phosphatase ,Fluorescence ,chemistry ,Positron emission tomography ,Positron-Emission Tomography ,Biophysics ,Nanoparticles ,Bioorthogonal chemistry ,Preclinical imaging ,HeLa Cells - Abstract
Pretargeted imaging has emerged as a promising approach to advance nuclear imaging of malignant tumors, however, the application of pretargeted strategy for multimodality imaging of enzyme activity in vivo is challenging. Herein, we combine the enzyme-mediated fluorogenic reaction and in situ self-assembly with the inverse electron demand Diels-Alder (IEDDA) reaction to develop an activatable pretargeted strategy for multimodality imaging. The trans -cyclooctene (TCO) bearing small-molecule probe, P-FFGd-TCO , can be activated by alkaline phosphatase and in situ self-assembles into nanoaggregates ( FMNPs-TCO ) retained on the membranes, permitting to (1) amplify near-infrared (NIR) fluorescence (FL) and magnetic resonance imaging (MRI) signals, and (2) enrich TCOs to promote IEDDA ligation. The Gallium-68 ( 68 Ga) labeled tetrazine can readily conjugate the tumor-retained FMNPs-TCO to enhance radioactivity uptake in tumors. Hence, strong NIR FL, MRI and positron emission tomography (PET) signals are concomitantly achieved, allowing for pretargeted multimodality imaging of ALP activity in HeLa tumor-bearing mice.
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- 2021
11. Degradable Hybrid CuS Nanoparticles for Imaging-Guided Synergistic Cancer Therapy via Low-Power NIR-II Light Excitation
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Deju Ye, Jian He, Zhengyang Zhou, Yuqi Wang, Xiaoyang Cheng, Yidan Sun, Hua Shi, Hong-Yuan Chen, and Luyan Wu
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Hyperthermia ,Materials science ,business.industry ,Radical ,Cancer therapy ,Nanoparticle ,General Chemistry ,Photochemistry ,medicine.disease ,Copper sulfide ,chemistry.chemical_compound ,chemistry ,medicine ,Light excitation ,Photonics ,business - Abstract
Near-infrared (NIR)-II light-excitable photonic agents capable of generating tumor hyperthermia and cytotoxic free radicals are promising for synergistic phototherapy of tumors. However, the lack o...
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- 2021
12. Manganese–Fluorouracil Metallodrug Nanotheranostic for MRI-Correlated Drug Release and Enhanced Chemoradiotherapy
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Haifeng Yuan, Yue Yang, Hong-Min Meng, Guosheng Song, Deju Ye, Xiao-Bing Zhang, Yuqi Wang, Shuangyan Huan, and Chan Yang
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Drug ,medicine.diagnostic_test ,business.industry ,media_common.quotation_subject ,Cancer therapy ,Magnetic resonance imaging ,General Chemistry ,Pharmacology ,Systemic toxicity ,Fluorouracil ,Drug delivery ,medicine ,Drug release ,business ,Chemoradiotherapy ,medicine.drug ,media_common - Abstract
For cancer therapy, drug delivery systems are often limited by insufficient drug loading capacity, which usually results in systemic toxicity and heavy metabolic burden to excrete the carriers. Her...
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- 2021
13. Tailoring a Near‐Infrared Macrocyclization Scaffold Allows the Control of In Situ Self‐Assembly for Photoacoustic/PET Bimodal Imaging
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Yuqi Wang, He Bai, Yinxing Miao, Jianhui Weng, Zheng Huang, Jiayu Fu, Yan Zhang, Jianguo Lin, and Deju Ye
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Photoacoustic Techniques ,Neoplasms ,Positron-Emission Tomography ,Humans ,Nanoparticles ,General Chemistry ,General Medicine ,Catalysis ,Fluorescent Dyes ,Molecular Imaging - Abstract
Enzyme-triggered macrocyclization and in situ self-assembly of small molecules into nanoparticles has shown promise to design activatable probes for molecular imaging. However, controlling macrocyclization and self-assembly to concurrently augment positron emission tomography (PET) and photoacoustic (PA) signals for bimodality imaging is challenging. Herein, we report the engineering of a triazole-IR780 fluorophore as a versatile macrocyclization scaffold for controlling in situ self-assembly and design a caspase-3-activatable PA/PET bimodal probe ([
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- 2022
14. Smart Magnetic and Fluorogenic Photosensitizer Nanoassemblies Enable Redox‐Driven Disassembly for Photodynamic Therapy
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Ruibing An, Shixuan Wei, Yidan Sun, Hong-Yuan Chen, Yuxuan Hu, Zheng Huang, Deju Ye, and Xiaoyang Cheng
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Photosensitizing Agents ,Chemistry ,medicine.medical_treatment ,Photodynamic therapy ,General Medicine ,General Chemistry ,Glutathione ,Small molecule ,Fluorescence ,Controlled release ,eye diseases ,Catalysis ,Magnetics ,chemistry.chemical_compound ,Photochemotherapy ,In vivo ,Cell Line, Tumor ,Neoplasms ,medicine ,Biophysics ,Animals ,Nanoparticles ,Photosensitizer ,Oxidation-Reduction ,Intracellular - Abstract
Stimuli-responsive smart photosensitizer (PS) nanoassemblies that allow enhanced delivery and controlled release of PSs are promising for imaging-guided photodynamic therapy (PDT) of tumors. However, the lack of high-sensitivity and spatial-resolution signals and fast washout of released PSs from tumor tissues have impeded PDT efficacy in vivo. Herein, we report tumor targeting, redox-responsive magnetic and fluorogenic PS nanoassemblies (NP-RGD) synthesized via self-assembly of a cRGD- and disulfide-containing fluorogenic and paramagnetic small molecule (1-RGD) for fluorescence/magnetic resonance bimodal imaging-guided tumor PDT. NP-RGD show high r1 relaxivity but quenched fluorescence and PDT activity; disulfide reduction by glutathione (GSH) promotes efficient disassembly into a small-molecule probe (2-RGD) and an organic PS (PPa-SH), which could further bind with intracellular albumin, allowing prolonged retention and cascade activation of fluorescence and PDT to ablate tumors.
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- 2020
15. An activatable ratiometric near-infrared fluorescent probe for hydrogen sulfide imaging in vivo
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Yuxuan Hu, Liandong Feng, Wenhui Zeng, Yingxiao Yan, Deju Ye, Hong-Yuan Chen, Yidan Sun, and Luyan Wu
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Materials science ,Hydrogen sulfide ,Near-infrared spectroscopy ,Nanoparticle ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Photochemistry ,01 natural sciences ,Fluorescence ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,In vivo ,Molecular imaging ,0210 nano-technology ,Nir fluorescence ,Preclinical imaging - Abstract
Ratiometric fluorescent probes hold great promise for in vivo imaging; however, stimuli-activatable ratiometric probes with fluorescence emissions in near-infrared (NIR) region are still very few. Herein, we report a hydrogen sulfide (H2S)-activatable ratiometric NIR fluorescent probe ( 1 -SPN) by integrating a H2S-responsive NIR fluorescent probe 1 into a H2S-inert poly[2,6-(4,4-bis-(2-ethylhexyl)-4 H -cyclopenta[2,1-b;3,4-b′]dithiophene)- alt -4,7(2,1,3-benzothiadiazole)] (PCPDTBT)-based NIR semiconducting polymer nanoparticle (SPN). 1 -SPN shows “always on” PCPDTBT fluorescence at 830 nm and weak probe 1 fluorescence at 725 nm under excitation at 680 nm. The ratio of NIR fluorescence intensities between 725 and 830 nm ( I 725/ I 830) is small. Upon interaction with H2S, the fluorescence at 725 nm is rapidly switched on, resulting in a large enhancement of I 725/ I 830, which is allowed for sensitive visualization and quantification of H2S concentrations in living cells. Taking advantage of enhanced tissue penetration depth of NIR fluorescence, 1 -SPN is also applied for real-time ratiometric fluorescence imaging of hepatic and tumor H2S in living mice. This study demonstrates that activatable ratiometric NIR fluorescent probes hold great potential for in vivo imaging.
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- 2020
16. NIR Scaffold Bearing Three Handles for Biocompatible Sequential Click Installation of Multiple Functional Arms
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Deju Ye, Yan Zhang, Yuqi Wang, Jianhui Weng, and Jianguo Lin
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Scaffold ,Biocompatible Materials ,Nanotechnology ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Catalysis ,Mice ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Animals ,neoplasms ,chemistry.chemical_classification ,Spectroscopy, Near-Infrared ,Biomolecule ,technology, industry, and agriculture ,General Chemistry ,equipment and supplies ,Biocompatible material ,Fluorescence ,0104 chemical sciences ,surgical procedures, operative ,chemistry ,Click chemistry ,Click Chemistry ,Azide - Abstract
Near-infrared (NIR) probes are ideal for fluorescence labeling and imaging of biological targets in living animals. However, the instability of common NIR dyes hampers the construction of NIR probes bearing multiple functional components such as biomolecules for specific targeting and imaging reagents for multimodality imaging. To overcome these limitations, we designed a novel NIR scaffold bearing two terminal alkynes as clickable handles and a chloride on the heptamethine backbone that allows nucleophilic substitution with an azide to generate the third clickable handle. This unique scaffold allows for facile installation of multiple functional arms for the construction of multifunctional NIR probes. Various biomacromolecules or imaging reagents can be introduced to the NIR scaffold by sequential one-pot click reactions under biocompatible conditions. The preclickable handle chloride on the NIR backbone does not interfere with the initial click reactions, and it can be easily transformed into an azide for a following click reaction. On the basis of this unique NIR scaffold, we developed a highly efficient method to construct diverse NIR probes containing multiple functional biomolecules including peptides, antibodies, nucleic acids, and NIR/PET (positron emission tomography) dual-modality imaging probes bearing tumor-targeting groups. NIR imaging or multimodality imaging using these probes was performed on live cells or tumor models on living mice.
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- 2020
17. Dehydroberberine Analogue Nanoassemblies for Inducing and Self-Reporting Mitochondrial Dysfunction in Tumor Cells
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Haifeng Sun, Zhanni Gu, Rui Zhang, Ruibing An, Deju Ye, and Hong Liu
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Berberine ,Molecular Structure ,Chemistry ,Cell Survival ,Biochemistry (medical) ,Biomedical Engineering ,Cancer ,Tumor cells ,Antineoplastic Agents ,Biocompatible Materials ,General Chemistry ,Mitochondrion ,medicine.disease ,Mitochondrial Dynamics ,Cell Line ,Mitochondria ,Biomaterials ,Materials Testing ,medicine ,Cancer research ,Humans ,Drug Screening Assays, Antitumor ,Particle Size - Abstract
Mitochondria-targeting probes that allow us to induce and report mitochondrial dysfunction have become promising theranostic agents for cancer; however, the lack of selectivity toward tumor cells over normal tissue cells has impeded the treatment outcome. Herein, we develop 10 fluorescent dehydroberberine derivatives (
- Published
- 2022
18. Design and Development of a Bioorthogonal, Visualizable and Mitochondria‐Targeted Hydrogen Sulfide (H 2 S) Delivery System
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Yong Liang, Deju Ye, Ruohan Zhao, Wenyuan Xu, Cheng Tang, Chun Zhang, Yuqi Wang, Luyan Wu, and Yinghan Chen
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chemistry.chemical_classification ,Hydrogen sulfide ,Substituent ,Alkyne ,General Chemistry ,General Medicine ,equipment and supplies ,Combinatorial chemistry ,Catalysis ,Cycloaddition ,chemistry.chemical_compound ,chemistry ,Thiophene ,Bioorthogonal chemistry ,Derivative (chemistry) ,Carbonyl sulfide - Abstract
Hydrogen sulfide (H2S) is an important endogenous gasotransmitter, but the targeted delivery and real-time feedback of exogenous H2S are still challenging. With the aid of density functional theory (DFT) calculations, we designed a new 1,3-dithiolium-4-olate (DTO) compound, which can react with a strained alkyne via the 1,3-dipolar cycloaddition and the retro-Diels-Alder reaction to generate carbonyl sulfide (COS) as the precursor of H2S, and a thiophene derivative with turn-on fluorescence. Moreover, the diphenylamino substituent in DTO greatly increases the mitochondrial targeting of this H2S delivery system. Such a bioorthogonal click-and-release reaction has integrated three functions in one system for the first time: (1) in-situ controllable H2S release, (2) concomitant fluorescence response, and (3) mitochondria-targeted delivery. In addition, we investigated the mitochondrial membrane potential loss alleviation by using this system in H9c2 cells under oxidative stress.
- Published
- 2021
19. An Activatable Afterglow/MRI Bimodal Nanoprobe with Fast Response to H 2 S for In Vivo Imaging of Acute Hepatitis
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Takanori Suzuki, Hong-Yuan Chen, Yuqi Wang, Wenhui Zeng, Deju Ye, Yuxuan Hu, Yusuke Ishigaki, Yidan Sun, Takashi Harimoto, and Luyan Wu
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biology ,Chemistry ,Cystathionine γ lyase ,Nanoprobe ,General Chemistry ,General Medicine ,Cystathionine beta synthase ,Catalysis ,Afterglow ,Nuclear magnetic resonance ,In vivo ,biology.protein ,Preclinical imaging ,Acute hepatitis - Abstract
Accurate detection of hepatic hydrogen sulfide (H 2 S) to monitor H 2 S-related enzymes' activity is critical for acute hepatitis diagnosis, but remains a challenge due to the dynamic and transient nature of H 2 S. Here, we report a H 2 S-activatable near-infrared afterglow/MRI bimodal probe F1 -GdNP, which shows an "always-on" MRI signal and "off-on" afterglow signal toward H 2 S. F1 -GdNP shows fast response, high sensitivity and specificity toward H 2 S, permitting afterglow imaging of H 2 S and evaluation of cystathionine γ -lyase's activity in living mice. We further employ the high spatial-resolution MRI signal of F1 -GdNP to track its delivery and accumulation in liver. Importantly, F1 -GdNP offers a high signal-to-background ratio (SBR = 86.2 ± 12.0) to sensitively report on the increased hepatic H 2 S level in the acute hepatitis mice via afterglow imaging, which correlated well with the upregulated CSE activity in the liver, showcasing the good potential of F1 -GdNP for monitoring of acute hepatitis process in vivo.
- Published
- 2021
20. An Activatable Near-Infrared Fluorescence Probe for in Vivo Imaging of Acute Kidney Injury by Targeting Phosphatidylserine and Caspase-3
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Deju Ye, Yan Zhang, Yuqi Wang, and Jianhui Weng
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Fluorescence-lifetime imaging microscopy ,Indoles ,Infrared Rays ,Mice, Nude ,Caspase 3 ,Apoptosis ,Phosphatidylserines ,urologic and male genital diseases ,Biochemistry ,Catalysis ,Cell Line ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,In vivo ,Coordination Complexes ,medicine ,Animals ,Fluorescent Dyes ,Cisplatin ,Kidney ,Mice, Inbred BALB C ,Optical Imaging ,Acute kidney injury ,General Chemistry ,Phosphatidylserine ,Acute Kidney Injury ,medicine.disease ,Acetylcysteine ,Zinc ,medicine.anatomical_structure ,chemistry ,Cancer research ,Female ,Preclinical imaging ,Biomarkers ,medicine.drug - Abstract
Renal-clearable and target-responsive near-infrared (NIR) fluorescent imaging probes have been promising for in vivo diagnosis of acute kidney injury (AKI). However, designing an imaging probe that is renal-clearable and concurrently responsive toward multiple molecular targets to facilitate early detection of AKI with improved sensitivity and specificity is challenging. Herein, by leveraging the receptor-mediated binding and retention effect along with enzyme-triggered fluorescence activation, we design and synthesize an activatable small-molecule NIR fluorescent probe (1-DPA2) using a "one-pot sequential click reaction" approach. 1-DPA2 can target both the externalized phosphatidylserine (PS) and active caspase-3 (Casp-3), two essential biomarkers of apoptosis, producing enhanced 808 nm NIR fluorescence and a high signal-to-background ratio (SBR) amenable to detecting the onset of cisplatin-induced AKI in mice as early as 24 h post-treatment with cisplatin. We not only monitor the gradual activation of Casp-3 in the kidney of mice upon AKI progression but also can report on the progressive recovery of kidney functions in AKI mice following N-acetyl-l-cysteine (NAC) therapy via real-time fluorescence imaging by 1-DPA2. This study demonstrates the ability of 1-DPA2 for longitudinal monitoring of renal cell apoptosis by concurrently targeting PS externalization and Casp-3 activation, which is efficient for early diagnosis of AKI and useful for prediction of potential drug nephrotoxicity as well as in vivo screening of anti-AKI drugs' efficacy.
- Published
- 2021
21. Generation of hydroxyl radical-activatable ratiometric near-infrared bimodal probes for early monitoring of tumor response to therapy
- Author
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Takashi Harimoto, Shiyi Liao, Takanori Suzuki, Deju Ye, Yinghan Chen, Pengfei Sun, Xiaobo Zhang, Ying Liu, Quli Fan, Yongchun Liu, Yong Liang, Guosheng Song, Yidan Sun, Wenhui Zeng, Luyan Wu, Yusuke Ishigaki, and Baoli Yin
- Subjects
Science ,medicine.medical_treatment ,General Physics and Astronomy ,Photochemistry ,Fluorescence ,Article ,General Biochemistry, Genetics and Molecular Biology ,Photoacoustic Techniques ,Mice ,chemistry.chemical_compound ,In vivo ,Cell Line, Tumor ,Neoplasms ,medicine ,Animals ,Ferroptosis ,chemistry.chemical_classification ,Reactive oxygen species ,Spectroscopy, Near-Infrared ,Multidisciplinary ,Hydroxyl Radical ,Optical Imaging ,Near-infrared spectroscopy ,General Chemistry ,Chromophore ,Molecular Imaging ,Radiation therapy ,chemistry ,Molecular Probes ,Cancer imaging ,Hydroxyl radical ,Biomedical materials ,Preclinical imaging - Abstract
Tumor response to radiotherapy or ferroptosis is closely related to hydroxyl radical (•OH) production. Noninvasive imaging of •OH fluctuation in tumors can allow early monitoring of response to therapy, but is challenging. Here, we report the optimization of a diene electrochromic material (1-Br-Et) as a •OH-responsive chromophore, and use it to develop a near-infrared ratiometric fluorescent and photoacoustic (FL/PA) bimodal probe for in vivo imaging of •OH. The probe displays a large FL ratio between 780 and 1113 nm (FL780/FL1113), but a small PA ratio between 755 and 905 nm (PA755/PA905). Oxidation of 1-Br-Et by •OH decreases the FL780/FL1113 while concurrently increasing the PA755/PA905, allowing the reliable monitoring of •OH production in tumors undergoing erastin-induced ferroptosis or radiotherapy., The hydroxyl radical is generated during radiotherapy and ferroptosis and accurate imaging of this reactive oxygen species may permit the monitoring of response to therapy. Here, the authors develop a ratiometric probe for accurate imaging of hydroxyl radical generation in vivo.
- Published
- 2021
22. Ultrasonic activation of inert poly(tetrafluoroethylene) enables piezocatalytic generation of reactive oxygen species
- Author
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Shangshang Dong, Zhenda Lu, Deju Ye, Di Wu, Guandao Gao, Wei Chen, Chad D. Vecitis, Peng Wang, Yeming Xu, Bingcai Pan, and Yanfeng Wang
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Materials science ,Piezoelectric coefficient ,Pollution remediation ,Science ,Sonication ,Radical ,General Physics and Astronomy ,Environmental pollution ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Article ,Catalysis ,General Biochemistry, Genetics and Molecular Biology ,chemistry.chemical_compound ,Inert ,Multidisciplinary ,Singlet oxygen ,General Chemistry ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,chemistry ,Chemical engineering ,Tetrafluoroethylene ,Electret ,0210 nano-technology ,Materials for energy and catalysis - Abstract
Controlled generation of reactive oxygen species (ROS) is essential in biological, chemical, and environmental fields, and piezoelectric catalysis is an emerging method to generate ROS, especially in sonodynamic therapy due to its high tissue penetrability, directed orientation, and ability to trigger in situ ROS generation. However, due to the low piezoelectric coefficient, and environmental safety and chemical stability concerns of current piezoelectric ROS catalysts, novel piezoelectric materials are urgently needed. Here, we demonstrate a method to induce polarization of inert poly(tetrafluoroethylene) (PTFE) particles ( ~ 1–5 μm) into piezoelectric electrets with a mild and convenient ultrasound process. Continued ultrasonic irradiation of the PTFE electrets generates ROS including hydroxyl radicals (•OH), superoxide (•O2−) and singlet oxygen (1O2) at rates significantly faster than previously reported piezoelectric catalysts. In summary, ultrasonic activation of inert PTFE particles is a simple method to induce permanent PTFE polarization and to piezocatalytically generate aqueous ROS that is desirable in a wide-range of applications from environmental pollution control to biomedical therapy., Controlled generation of reactive oxygen species (ROS) is essential in biological, chemical, and environmental fields. Here, the authors report that ultrasonication can induce polarization of inert poly(tetrafluoroethylene) to a piezoelectric electret and drive piezocatalytic generation of aqueous ROS.
- Published
- 2021
23. Plasmonic Nanohybrid with High Photothermal Conversion Efficiency for Simultaneously Effective Antibacterial/Anticancer Photothermal Therapy
- Author
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Rui Bing An, Muhammad Rizwan Younis, Deju Ye, Yun-Chao Yin, Shouju Wang, and Xing-Hua Xia
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Laser power density ,Materials science ,business.industry ,Biochemistry (medical) ,Biomedical Engineering ,Nanotechnology ,General Chemistry ,Photothermal therapy ,Biomaterials ,Semiconductor ,Photocatalysis ,business ,Biosensor ,Plasmon - Abstract
Plasmonic metal/semiconductor nanohybrids hold great promise in photocatalysis and biosensor development; however, their potential phototherapeutic applications are yet fully unexplored. On the other hand, the demand of high laser power density to induce antibacterial photothermal therapeutic effects greatly restricts the practical applicability of the previously developed photothermal nanoagents (PTAs) for anticancer photothermal therapy (PTT). Here, we develop a plasmonic nanohybrid by integrating plasmonic noble metal gold nanorods (AuNRs) with a two-dimensional graphene oxide (2-D GO), capable to perform photothermal ablation of both bacterial pathogens as well as tumor cells, respectively, under low power single near-infrared (NIR) laser activation. Owing to the synergistic plasmonic photothermal effect (PPTT) of dual plasmonic PTAs, the plasmonic AuNR/GO nanohybrid exhibits remarkably higher photothermal conversion efficiency (PCE, 72.59%) than either individual AuNRs or GO under low laser power density (300 mW), leading to enhanced antibacterial/anticancer PTT. In addition, the synergistic plasmonic antibacterial/anticancer PTT induced by the plasmonic nanohybrid is also far superior to individual PTAs (AuNRs or GO), whereas the flow cytometric analysis of heat shock proteins (HSP 70) clearly dictates that the substantial killing of bacterial pathogens/tumor cells is solely due to the synergistic PPTT. Thus, the plasmonic AuNR/GO nanohybrid is a standalone PTA to perform simultaneous antibacterial/anticancer PTT under low power NIR laser activation for only 5 min, without any systemic side effects. The present study provides a clear demonstration about the potential therapeutic impact of plasmonic nanohybrids and thus will surely pave the way to design other hybrid nanoagents with enhanced PCE and integrate them with chemotherapeutic agents, leading to dual-modal chemo-/photothermal antibacterial/anticancer therapy under low power single laser excitation for a short duration.
- Published
- 2019
24. Activatable NIR Fluorescence/MRI Bimodal Probes for in Vivo Imaging by Enzyme-Mediated Fluorogenic Reaction and Self-Assembly
- Author
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Hong Liu, Yuxuan Hu, Runqi Yan, Fei Liu, Shixuan Wei, Deju Ye, Daqing Fang, Adam J. Shuhendler, and Hong-Yuan Chen
- Subjects
In situ ,Infrared Rays ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Fluorescence ,Catalysis ,Small Molecule Libraries ,Mice ,Colloid and Surface Chemistry ,Tissue engineering ,medicine ,Animals ,Humans ,Cells, Cultured ,Fluorescent Dyes ,Molecular Structure ,medicine.diagnostic_test ,Chemistry ,Optical Imaging ,Magnetic resonance imaging ,Hep G2 Cells ,General Chemistry ,Alkaline Phosphatase ,Magnetic Resonance Imaging ,Small molecule ,0104 chemical sciences ,HEK293 Cells ,Biophysics ,Alkaline phosphatase ,Molecular imaging ,Preclinical imaging ,HeLa Cells - Abstract
Stimuli-responsive in situ self-assembly of small molecules to form nanostructures in living subjects has produced promising tools for molecular imaging and tissue engineering. However, controlling the self-assembly process to simultaneously activate multimodality imaging signals in a small-molecule probe is challenging. In this paper, we rationally integrate a fluorogenic reaction into enzyme-responsive in situ self-assembly to design small-molecule-based activatable near-infrared (NIR) fluorescence and magnetic resonance (MR) bimodal probes for molecular imaging. Using alkaline phosphatase (ALP) as a model target, we demonstrate that probe (P-CyFF-Gd) can be activated by endogenous ALP overexpressed on cell membranes, producing membrane-localized assembled nanoparticles (NPs) that can be directly visualized by cryo-SEM. Simultaneous enhancements in NIR fluorescence (>70-fold at 710 nm) and r1 relaxivity (∼2.3-fold) enable real-time, high-sensitivity, high-spatial-resolution imaging and localization of the ALP activity in live tumor cells and mice. P-CyFF-Gd can also delineate orthotopic liver tumor foci, facilitating efficient real-time, image-guided surgical resection of tumor tissues in intraoperative mice. This strategy combines activatable NIR fluorescence via a fluorogenic reaction and activatable MRI via in situ self-assembly to promote ALP activity imaging, which could be applicable to design other activatable bimodal probes for in vivo imaging of enzyme activity and locations in real time.
- Published
- 2019
25. A Photoacoustic Probe for the Imaging of Tumor Apoptosis by Caspase‐Mediated Macrocyclization and Self‐Assembly
- Author
-
Jianhui Weng, Deju Ye, Jinbo Li, Quli Fan, Xiaoming Hu, Yuqi Wang, and Yan Zhang
- Subjects
Macrocyclic Compounds ,medicine.medical_treatment ,Photoacoustic imaging in biomedicine ,Caspase 3 ,Apoptosis ,010402 general chemistry ,Cleavage (embryo) ,01 natural sciences ,Catalysis ,Photoacoustic Techniques ,medicine ,Distribution (pharmacology) ,Humans ,Caspase ,Chemotherapy ,biology ,Molecular Structure ,010405 organic chemistry ,Chemistry ,Optical Imaging ,General Chemistry ,General Medicine ,0104 chemical sciences ,Molecular Imaging ,Cyclization ,Caspases ,Molecular Probes ,biology.protein ,Cancer research ,Imaging Signal ,Glioblastoma - Abstract
Photoacoustic (PA) imaging shows promise in the sensitive detection of caspase-3 activated in early tumor apoptosis in response to chemotherapy; smart PA probes are thus in high demand. Herein, we report the first smart PA probe (1-RGD) responsive to caspase-3, enabling real-time and high-resolution imaging of tumor apoptosis. 1-RGD is designed to leverage the synergetic effect of active delivery and caspase-3 activation. It is selectively recognized by active caspase-3 to trigger peptide substrate cleavage and biocompatible macrocyclization-mediated self-assembly, leading to an amplified PA imaging signal and prolonged retention in apoptotic tumor cells. Strong, high-resolution PA images are obtained in chemotherapy-induced apoptotic tumors in living mice after intravenous administration with 1-RGD, facilitating sensitive reporting of caspase-3 activity and distribution within tumor tissues.
- Published
- 2019
26. Magnetic Semiconductor Gd-Doping CuS Nanoparticles as Activatable Nanoprobes for Bimodal Imaging and Targeted Photothermal Therapy of Gastric Tumors
- Author
-
Zhengyang Zhou, Runqi Yan, Hua Shi, Yidan Sun, Yuzhang Feng, Shunli Liu, Song Liu, Deju Ye, Jian He, Peng Wang, and Li Zhu
- Subjects
Fluorescence-lifetime imaging microscopy ,Materials science ,Nanoprobe ,Gadolinium ,Bioengineering ,02 engineering and technology ,Theranostic Nanomedicine ,Metastasis ,Mice ,Nuclear magnetic resonance ,Stomach Neoplasms ,Quantum Dots ,medicine ,Animals ,General Materials Science ,medicine.diagnostic_test ,Mechanical Engineering ,Optical Imaging ,Magnetic resonance imaging ,Hyperthermia, Induced ,General Chemistry ,Phototherapy ,Photothermal therapy ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,medicine.disease ,Magnetic Resonance Imaging ,Fluorescence ,Cancer cell ,Magnets ,Matrix Metalloproteinase 2 ,Molecular imaging ,0210 nano-technology ,Copper - Abstract
Targeted delivery of enzyme-activatable probes into cancer cells to facilitate accurate imaging and on-demand photothermal therapy (PTT) of cancers with high spatiotemporal precision promises to advance cancer diagnosis and therapy. Here, we report a tumor-targeted and matrix metalloprotease-2 (MMP-2)-activatable nanoprobe (T-MAN) formed by covalent modification of Gd-doping CuS micellar nanoparticles with cRGD and an MMP-2-cleavable fluorescent substrate. T-MAN displays a high r1 relaxivity (∼60.0 mM–1 s–1 per Gd3+ at 1 T) and a large near-infrared (NIR) fluorescence turn-on ratio (∼185-fold) in response to MMP-2, allowing high-spatial-resolution magnetic resonance imaging (MRI) and low-background fluorescence imaging of gastric tumors as well as lymph node (LN) metastasis in living mice. Moreover, T-MAN has a high photothermal conversion efficiency (PCE, ∼70.1%) under 808 nm laser irradiation, endowing it with the ability to efficiently generate heat to kill tumor cells. We demonstrate that T-MAN can ac...
- Published
- 2019
27. Ratiometric Imaging of MMP-2 Activity Facilitates Tumor Detection Using Activatable Near-Infrared Fluorescent Semiconducting Polymer Nanoparticles
- Author
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Deju Ye, Luyan Wu, Jinfang Wang, Yuqi Wang, Wenhui Zeng, and Yidan Sun
- Subjects
Fluorophore ,Polymers ,Near-infrared spectroscopy ,Optical Imaging ,Nanoparticle ,General Chemistry ,Semiconducting polymer ,Fluorescence ,Ratiometric fluorescence ,Biomaterials ,chemistry.chemical_compound ,chemistry ,In vivo ,Stomach Neoplasms ,Biophysics ,Humans ,Matrix Metalloproteinase 2 ,Nanoparticles ,General Materials Science ,Preclinical imaging ,Biotechnology - Abstract
Enzyme-activatable ratiometric near-infrared (NIR) fluorescent probes enabling noninvasive imaging of enzyme activity in vivo are promising for biomedical research; however, such probes with ratiometric fluorescence emissions both in NIR window under a single NIR light excitation are largely unexplored. Here, a quenched NIR fluorophore of Cy5.5 is integrated with NIR fluorescent poly[2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b']dithiophene)-alt-4,7(2,1,3-benzothiadiazole)] (PCPDTBT)-based semiconducting polymer nanoparticles (SPNs), and an αv β3 integrin-targeting and matrix metalloproteinase-2 (MMP-2)-activatable ratiometric fluorescent probe (SPN-MMP-RGD) is developed. Under excitation at 660 nm, SPN-MMP-RGD shows "always-on" fluorescence of PCPDTBT (830 nm) and activatable fluorescence of Cy5.5 (690 nm) toward MMP-2, affording a remarkable ≈176-fold enhancement in fluorescence intensity ratio between 690 and 830 nm (I690 /I830 ) for sensitive detection of MMP-2 activity in vitro and in tumor cells. By virtue of ratiometric fluorescence imaging independently of probe's concentration, SPN-MMP-RGD can not only accurately report on MMP-2 levels regarding different tumor sizes, but also noninvasively delineate MMP-2-positive tiny gastric tumors metastasis in vivo. The authors' study reveals the potential of SPN-MMP-RGD for ratiometric fluorescence imaging of MMP-2 activity via combining two independent NIR fluorophores, which can be amenable for the design of other enzyme-activatable ratiometric NIR fluorescent probes for reliable in vivo imaging.
- Published
- 2021
28. H2S-activatable near-infrared afterglow luminescent probes for sensitive molecular imaging in vivo
- Author
-
Takanori Suzuki, Deju Ye, Jian He, Xiqun Jiang, Luyan Wu, Takashi Harimoto, Yuxuan Hu, Yidan Sun, Yusuke Ishigaki, Wenhui Zeng, Hong-Yuan Chen, and Keisuke Sugimoto
- Subjects
Carcinoma, Hepatocellular ,Vinyl Compounds ,Polymers ,Science ,Cystathionine beta-Synthase ,General Physics and Astronomy ,Nanoparticle ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Article ,General Biochemistry, Genetics and Molecular Biology ,Liver Neoplasms, Experimental ,Nuclear magnetic resonance ,In vivo ,Animals ,Humans ,Photosensitizer ,Hydrogen Sulfide ,lcsh:Science ,Mice, Inbred BALB C ,Luminescent Agents ,Photosensitizing Agents ,Multidisciplinary ,Chemistry ,Liver Neoplasms ,Near-infrared spectroscopy ,Cystathionine gamma-Lyase ,Bioanalytical chemistry ,Hep G2 Cells ,General Chemistry ,equipment and supplies ,021001 nanoscience & nanotechnology ,Xenograft Model Antitumor Assays ,Molecular Imaging ,0104 chemical sciences ,Afterglow ,Nanoparticles ,lcsh:Q ,Molecular imaging ,Colorectal Neoplasms ,0210 nano-technology ,Luminescence ,Preclinical imaging - Abstract
Afterglow luminescent probes with high signal-to-background ratio show promise for in vivo imaging; however, such probes that can be selectively delivered into target sites and switch on afterglow luminescence remain limited. We optimize an organic electrochromic material and integrate it into near-infrared (NIR) photosensitizer (silicon 2,3-naphthalocyanine bis(trihexylsilyloxide) and (poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene]) containing nanoparticles, developing an H2S-activatable NIR afterglow probe (F12+-ANP). F12+-ANP displays a fast reaction rate (1563 ± 141 M−1 s−1) and large afterglow turn-on ratio (~122-fold) toward H2S, enabling high-sensitivity and -specificity measurement of H2S concentration in bloods from healthy persons, hepatic or colorectal cancer patients. We further construct a hepatic-tumor-targeting and H2S-activatable afterglow probe (F12+-ANP-Gal) for noninvasive, real-time imaging of tiny subcutaneous HepG2 tumors (, Afterglow imaging probes are of interest for in vivo imaging due to high signal-to-background ratios. Here, the authors report on an afterglow nanoparticle which is activated by hydrogen sulphide and demonstrate the measurement of hydrogen sulphide levels and the labelling of hepatic cancer specimens in vivo.
- Published
- 2020
29. Hexaarylbutadiene: A Versatile Scaffold with Tunable Redox Properties towards Organic Near-Infrared Electrochromic Material
- Author
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Luyan Wu, Takanori Suzuki, Keisuke Sugimoto, Deju Ye, Wenhui Zeng, Yusuke Ishigaki, and Takashi Harimoto
- Subjects
010405 organic chemistry ,Aryl ,Organic Chemistry ,Near-infrared spectroscopy ,General Chemistry ,010402 general chemistry ,Photochemistry ,01 natural sciences ,Biochemistry ,Redox ,0104 chemical sciences ,chemistry.chemical_compound ,Aniline ,chemistry ,Electrochromism ,Halogen ,Cyclic voltammetry ,Absorption (chemistry) - Abstract
When the 1,1,4,4-tetraanilinobutadiene skeleton is attached with two halogenated aryl units at the 2,3-positions, they undergo facile two-electron oxidation to give stable dicationic dyes which exhibit a near-infrared (NIR) absorption whereas the neutral dienes show only pale color. Therefore, a distinct electrochromic response with an absorption change in the NIR region is achieved, which is attracting considerable recent attention from the viewpoint of bioimaging. Herein, we demonstrate that the redox potentials of the 1,1,4,4-tetraanilinobutadiene can be precisely controlled by the donating properties of the amino group on the aniline unit as well as the number of halogen atoms on the aryl units at 2,3-positions on the butadiene. In contrast, the NIR absorption bands mainly depend on the number of halogen atoms irrespective to the donating properties of aniline unit. Thus, the hexaarylbutadiene skeleton is proven to be a versatile scaffold to develop less-explored organic NIR electrochromic materials, whose redox and spectroscopic properties can be finely tuned by modifying/attaching the proper substituents.
- Published
- 2019
30. Firefly Luciferin-Inspired Biocompatible Chemistry for Protein Labeling and In Vivo Imaging
- Author
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Deju Ye, Yuqi Wang, Ruibing An, and Zhiliang Luo
- Subjects
Nanotechnology ,Firefly luciferin ,Firefly Luciferin ,010402 general chemistry ,Protein labeling ,01 natural sciences ,Catalysis ,Mice ,chemistry.chemical_compound ,Luciferases, Firefly ,Nitriles ,Animals ,Bioluminescence ,Benzothiazoles ,Cysteine ,Firefly protocol ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Proteins ,General Chemistry ,Biocompatible material ,Luciferin ,Molecular Imaging ,0104 chemical sciences ,Caspases ,Molecular imaging ,Cyclobutanes ,Preclinical imaging - Abstract
Biocompatible reactions have emerged as versatile tools to build various molecular imaging probes that hold great promise for the detection of biological processes in vitro and/or in vivo. In this Minireview, we describe the recent advances in the development of a firefly luciferin-inspired biocompatible reaction between cyanobenzothiazole (CBT) and cysteine (Cys), and highlight its versatility to label proteins and build multimodality molecular imaging probes. The review starts from the general introduction of biocompatible reactions, which is followed by briefly describing the development of the firefly luciferin-inspired biocompatible chemistry. We then discuss its applications for the specific protein labeling and for the development of multimodality imaging probes (fluorescence, bioluminescence, MRI, PET, photoacoustic, etc.) that enable high sensitivity and spatial resolution imaging of redox environment, furin and caspase-3/7 activity in living cells and mice. Finally, we offer the conclusions and our perspective on the various and potential applications of this reaction. We hope that this review will contribute to the research of biocompatible reactions for their versatile applications in protein labeling and molecular imaging.
- Published
- 2017
31. Dual Stimuli-Responsive Nanoparticles for Controlled Release of Anticancer and Anti-inflammatory Drugs Combination
- Author
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Zheng Huang, Zhiliang Luo, Yuqi Wang, Liandong Feng, Kai Guo, Yan Zhang, and Deju Ye
- Subjects
Drug ,Cell Survival ,Polymers ,media_common.quotation_subject ,Indomethacin ,Anti-Inflammatory Agents ,Antineoplastic Agents ,02 engineering and technology ,Pharmacology ,010402 general chemistry ,01 natural sciences ,Catalysis ,Mice ,Folic Acid ,medicine ,Animals ,Humans ,Doxorubicin ,media_common ,Drug Carriers ,Microscopy, Confocal ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Chemistry ,Macrophages ,Organic Chemistry ,Rational design ,General Chemistry ,Hydrogen-Ion Concentration ,021001 nanoscience & nanotechnology ,Controlled release ,0104 chemical sciences ,G2 Phase Cell Cycle Checkpoints ,Multiple drug resistance ,Drug Liberation ,HEK293 Cells ,RAW 264.7 Cells ,Targeted drug delivery ,Cyclooxygenase 2 ,Drug delivery ,Cancer cell ,MCF-7 Cells ,Nanoparticles ,0210 nano-technology ,HeLa Cells ,medicine.drug - Abstract
Dual stimuli-responsive nanoparticles capable of fine-tuning drug release to augment therapeutic efficacy have become a promising tool for anticancer drug delivery. However, the rational design of these "smart" nanoparticles for a selective delivery and controlled release of multidrug combinations in cancer cells to achieve synergistic effects remain challenging. Here we report the pH/redox dual responsive nanoparticle FA-DOX-Ind-NP (FA=folic acid, DOX=doxorubicin, Ind=indomethacin, NP=nanoparticle) based on the novel tumor targeting and biodegradable poly(β-amino ester) polymer, and demonstrate its high ability to enter into cancer cells and release a combination of the anticancer drug doxorubicin and the non-steroidal anti-inflammatory drug indomethacin to achieve synergistic chemo-anti-inflammatory effects and overcome multidrug resistance. This study highlights the great potential of tumor targeting and dual stimuli-responsive nanoparticles for an efficient delivery of multidrug combination to improve the cancer therapeutic efficacy.
- Published
- 2017
32. Engineering of Electrochromic Materials as Activatable Probes for Molecular Imaging and Photodynamic Therapy
- Author
-
Deju Ye, Zhiliang Luo, Hong-Yuan Chen, Kanyi Pu, Takanori Suzuki, Yidan Sun, Keisuke Sugimoto, Luyan Wu, Yusuke Ishigaki, and School of Chemical and Biomedical Engineering
- Subjects
Polymers ,medicine.medical_treatment ,Nanoparticle ,Photodynamic therapy ,02 engineering and technology ,Photochemistry ,01 natural sciences ,Biochemistry ,Mice ,Colloid and Surface Chemistry ,Neoplasms ,Stilbenes ,Photosensitizer ,Hydrogen Sulfide ,chemistry.chemical_classification ,Mice, Inbred BALB C ,Aniline Compounds ,Photosensitizing Agents ,Singlet Oxygen ,Chemistry ,Chemical engineering [Engineering] ,Polymer ,021001 nanoscience & nanotechnology ,Fluorescence ,Molecular Imaging ,Liver ,Electrochromism ,Female ,Anatomy ,0210 nano-technology ,Vinyl Compounds ,Infrared Rays ,010402 general chemistry ,Catalysis ,Cell Line, Tumor ,Thiadiazoles ,medicine ,Animals ,Humans ,Fluorescent Dyes ,General Chemistry ,Chromophore ,Xenograft Model Antitumor Assays ,0104 chemical sciences ,HEK293 Cells ,RAW 264.7 Cells ,Photochemotherapy ,Drug Design ,Nanoparticles ,Molecular imaging - Abstract
Electrochromic materials (EMs) are widely used color-switchable materials, but their applications as stimuli-responsive biomaterials to monitor and control biological processes remain unexplored. This study reports the engineering of an organic π-electron structure-based EM (dicationic 1,1,4,4-tetraarylbutadiene, 12+) as a unique hydrogen sulfide (H2S)-responsive chromophore amenable to build H2S-activatable fluorescent probes (12+-semiconducting polymer nanoparticles, 12+-SNPs) for in vivo H2S detection. We demonstrate that EM 12+, with a strong absorption (500–850 nm), efficiently quenches the fluorescence (580, 700, or 830 nm) of different fluorophores within 12+-SNPs, while the selective conversion into colorless diene 2 via H2S-mediated two-electron reduction significantly recovers fluorescence, allowing for non-invasive imaging of hepatic and tumor H2S in mice in real time. Strikingly, EM 12+ is further applied to design a near-infrared photosensitizer with tumor-targeting and H2S-activatable ability for effective photodynamic therapy (PDT) of H2S-related tumors in mice. This study demonstrates promise for applying EMs to build activatable probes for molecular imaging of H2S and selective PDT of tumors, which may lead to the development of new EMs capable of detecting and regulating essential biological processes in vivo.
- Published
- 2018
33. Frontispiece: Firefly Luciferin-Inspired Biocompatible Chemistry for Protein Labeling and In Vivo Imaging
- Author
-
Deju Ye, Yuqi Wang, Ruibing An, and Zhiliang Luo
- Subjects
chemistry.chemical_compound ,chemistry ,Organic Chemistry ,Biophysics ,Firefly luciferin ,General Chemistry ,Molecular imaging ,Biocompatible material ,Protein labeling ,Luciferin ,Catalysis ,Preclinical imaging - Published
- 2018
34. Self-assembly of Fluorescent Dehydroberberine Enhances Mitochondria-Dependent Antitumor Efficacy
- Author
-
Runqi Yan, Ruibing An, Hong Liu, Haifeng Sun, Deju Ye, Zhanni Gu, and Yuxuan Hu
- Subjects
Fluorescence-lifetime imaging microscopy ,Berberine ,Stacking ,Nanoparticle ,Antineoplastic Agents ,02 engineering and technology ,Mitochondrion ,010402 general chemistry ,01 natural sciences ,Catalysis ,chemistry.chemical_compound ,Mice ,In vivo ,Animals ,Fluorescent Dyes ,Chemistry ,Organic Chemistry ,General Chemistry ,021001 nanoscience & nanotechnology ,Fluorescence ,0104 chemical sciences ,Mitochondria ,Biophysics ,Self-assembly ,0210 nano-technology - Abstract
Selective imaging and inducing mitochondrial dysfunction in tumor cells using mitochondria-targeting probes has become as a promising approach for cancer diagnosis and therapy. Here, we report the design of a fluorescent berberine analog, dehydroberberine (DH-BBR), as a new mitochondria-targeting probe capable of self-assembling into monodisperse organic nanoparticles (DTNPs) upon integration with a lipophilic counter anion, allowing for enhanced fluorescence imaging and treatment of tumors in living mice. X-ray crystallography revealed that the self-assembly process was attributed to a synergy of different molecular interactions, including π-π stacking, O⋅⋅⋅π interaction and electrostatic interaction between DH-BBR and counter anions. We demonstrated that DTNPs could efficiently enter tumor tissue following intravenous injection and enhance mitochondrial delivery of DH-BBR via an electrostatic interaction driven anion exchange process. Selective accumulation in the mitochondria capable of emitting strong fluorescence and causing mitochondrial dysfunction was achieved, enabling efficient inhibition of tumor growth in living mice. This study demonstrates promise for applying lipophilic anions to control molecular self-assembly and tune antitumor activity of mitochondria-targeting probes, which can facilitate to improve cancer treatment in vivo.
- Published
- 2018
35. Cysteine-Mediated Intracellular Building of Luciferin to Enhance Probe Retention and Fluorescence Turn-On
- Author
-
Haixiao Huang, Mi Zhou, Hong-Yuan Chen, Yuqi Wang, Deju Ye, Yan Zhang, and Mengmeng Zheng
- Subjects
Endogeny ,Fluorescence ,Catalysis ,HeLa ,Humans ,Benzothiazoles ,Cysteine ,Sulfhydryl Compounds ,chemistry.chemical_classification ,biology ,Chemistry ,Organic Chemistry ,Mesenchymal Stem Cells ,General Chemistry ,biology.organism_classification ,Glutathione ,Luciferin ,Amino acid ,Oxidative Stress ,Acrylates ,Biochemistry ,Biophysics ,Molecular probe ,Biosensor ,Intracellular ,HeLa Cells - Abstract
The development of sensitive and selective small molecular probes that enable real-time detection of endogenous cysteine (Cys) has become an attractive topic because of the essential roles played by Cys in controlling the cellular nitrogen balance and in maintaining biological redox homeostasis. Herein, we report a Cys-specific probe, 2-cyanobenzothiazol-6-yl acrylate (CBTOA), that shows not only fluorescence turn-on for sensitive detection of endogenous Cys but also enhanced probe retention inside cells for real-time monitoring of Cys levels upon external stimulation. Cys-mediated intracellular formation of luciferin from CBTOA was the key strategy leading to this new type of fluorogenic probe. CBTOA showed fast response to Cys in living cells and liver tissue slices with high sensitivity and selectivity. By using CBTOA as a real-time probe, we were able to monitor the change in Cys levels in living HeLa cells under ROS-induced oxidative stress as well as in human mesenchymal stem cells during adipogenic differentiation.
- Published
- 2015
36. Simultaneous quantification of multiple endogenous biothiols in single living cells by plasmonic Raman probes
- Author
-
Bin Kang, Yuqi Wang, Deju Ye, Shanshan Li, Hong-Yuan Chen, Mengmeng Zheng, Jing-Juan Xu, and Qi-Yuan Guan
- Subjects
chemistry.chemical_classification ,Lysis ,biology ,Biomolecule ,technology, industry, and agriculture ,02 engineering and technology ,General Chemistry ,Glutathione ,010402 general chemistry ,021001 nanoscience & nanotechnology ,biology.organism_classification ,01 natural sciences ,In vitro ,0104 chemical sciences ,HeLa ,chemistry.chemical_compound ,Chemistry ,chemistry ,Biochemistry ,In vivo ,0210 nano-technology ,Intracellular ,Cysteine - Abstract
Three endogenous biothiols in single cells were simultaneously quantified by plasmonic Raman probes and quantitative principal component analysis (qPCA)., Intracellular biothiols mediate many important physiological and pathological processes. Due to their low content and competing thiol-reactivity, it is still an unmet challenge to quantify them within a complicated intracellular environment. Herein, we demonstrated a strategy to discriminate three biothiols, i.e. cysteine (Cys), homo-cysteine (Hcy) and glutathione (GSH), and quantify their concentrations within single living cells, using one platform of Raman probe. By monitoring the reaction kinetics of biothiols with Raman probes and discriminating their products with a quantitative principal component analysis (qPCA) method, these three biothiols could be simultaneously quantified in both cell lysis and single living cells. The concentrations of Cys, Hcy and GSH in single Hela cells were 158 ± 19 μM, 546 ± 67 μM and 5.07 ± 0.62 mM, respectively, which gives the precise concentrations of these three biothiols at a single cell level for the first time. This method provides a general strategy for discriminating each component from a mixed system and has potential for quantifying any biomolecules within an in vitro or in vivo biological environment.
- Published
- 2017
37. Activatable Near-Infrared Probe for Fluorescence Imaging of γ-Glutamyl Transpeptidase in Tumor Cells and In Vivo
- Author
-
Guanfu Duan, Hua Shi, Changge Ji, Runqi Yan, Ruibing An, Hong-Yuan Chen, Zhiliang Luo, Liandong Feng, Deju Ye, Jian He, and Zhengyang Zhou
- Subjects
Fluorescence-lifetime imaging microscopy ,Fluorophore ,Indoles ,Transplantation, Heterologous ,Mice, Nude ,02 engineering and technology ,010402 general chemistry ,digestive system ,01 natural sciences ,Catalysis ,chemistry.chemical_compound ,Mice ,In vivo ,Cell Line, Tumor ,Neoplasms ,Animals ,Humans ,Merocyanine ,Benzopyrans ,Benzyl Alcohols ,Fluorescent Dyes ,chemistry.chemical_classification ,Spectroscopy, Near-Infrared ,Organic Chemistry ,Near-infrared spectroscopy ,General Chemistry ,gamma-Glutamyltransferase ,021001 nanoscience & nanotechnology ,HCT116 Cells ,Fluorescence ,digestive system diseases ,0104 chemical sciences ,Enzyme ,chemistry ,Biochemistry ,Microscopy, Fluorescence ,Biophysics ,Female ,0210 nano-technology ,Linker - Abstract
γ-Glutamyl transpeptidase (GGT) is a cell-membrane-bound enzyme that is involved in various physiological and pathological processes and is regarded as a potential biomarker for many malignant tumors, precise detection of which is useful for early cancer diagnosis. Herein, a new GGT-activatable near-infrared (NIR) fluorescence imaging probe (GANP) by linking of a GGT-recognitive substrate γ-glutamate (γ-Glu) and a NIR merocyanine fluorophore (mCy-Cl) with a self-immolative linker p-aminobenzyl alcohol (PABA) is reported. GANP was stable under physiological conditions, but could be efficiently activated by GGT to generate ≈100-fold enhanced fluorescence, enabling high sensitivity (detection limit of ≈3.6 mU L-1 ) and specificity for the real-time imaging of GGT activity as well as rapid evaluation of the inhibition efficacy of GGT inhibitors in living tumor cells. Notably, the deep tissue penetration ability of NIR fluorescence could further allow GANP to image GGT in frozen tumor tissue slices with large penetration depth (>100 μm) and in xenograft tumors in living mice. This GGT activatable NIR fluorescence imaging probe could facilitate the study and diagnosis of other GGT-correlated diseases in vivo.
- Published
- 2017
38. Two-photon excitation nanoparticles for photodynamic therapy
- Author
-
Yizhong Shen, Jing-Juan Xu, Hong-Yuan Chen, Deju Ye, and Adam J. Shuhendler
- Subjects
Materials science ,Light ,Polymers ,medicine.medical_treatment ,Nanoparticle ,Metal Nanoparticles ,Photodynamic therapy ,Nanotechnology ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Nanomaterials ,chemistry.chemical_compound ,Two-photon excitation microscopy ,Neoplasms ,medicine ,Animals ,Humans ,Absorption (electromagnetic radiation) ,Photosensitizing Agents ,Singlet oxygen ,General Chemistry ,021001 nanoscience & nanotechnology ,Silicon Dioxide ,Carbon ,0104 chemical sciences ,chemistry ,Photochemotherapy ,Quantum dot ,Nanoparticles ,Gold ,0210 nano-technology ,Visible spectrum - Abstract
Two-photon excitation (TPE) nanoparticle-based photosensitizers (PSs) that combine the advantages of TPE and nanotechnology have emerged as attractive therapeutic agents for near-infrared red (NIR) light excited photodynamic therapy (PDT) for cancer treatment. TPE PDT is characterized by nonlinear absorption of two relatively low-energy photons of NIR light with the resulting emission of high-energy visible light. This high-energy light can sensitize oxygen to produce cytotoxic reactive oxygen species (ROS) and singlet oxygen (1O2) which can kill cancer cells. The long-wavelength light used to excite TPE NPs allows for deeper tissue penetration to achieve efficient PDT of deep-seated tumors. Moreover, TPE nanoparticles normally have large two-photon absorption (TPA) cross-sections, which hold great potential as efficient two-photon donors in PDT. In this review, we will summarize the recent advances made in the development of TPE nanoparticles for cancer PDT. Five different TPE nanoparticles, including quantum dots (QDs), carbon nanomaterials, silica nanoparticles, gold nanomaterials, and polymer nanoparticles, are summarized in detail, and the existing challenges as well as the future perspectives are also discussed.
- Published
- 2016
39. An Effective Synthetic Entry to Fused Benzimidazoles via Iodocyclization
- Author
-
Yu Zhou, Diliang Guo, Hengshuai Wang, Hualiang Jiang, Xu Zhang, Yungen Xu, Deju Ye, and Hong Liu
- Subjects
chemistry.chemical_classification ,Chemistry ,chemistry.chemical_element ,Alkyne ,General Chemistry ,Iodine ,Chemical synthesis ,chemistry.chemical_compound ,Silver nitrate ,Polycyclic compound ,Yield (chemistry) ,Organic chemistry ,Piperidine ,Pyrrole - Abstract
A protocol for the synthesis of the fused heterocyclic polycyclic compounds pyrrole[1,2-a]benzimidazoles, piperidine[1,2-a]benzimidazoles and oxa-fused benzimidazoles using iodine and silver nitrate by an exo-dig or endo-dig cyclization pathway at room temperature has been developed. Silver nitrate is a key additive for improving the yield, and the improvement is a result of this additive eliminating the influence of iodine ions (I ― ), which would otherwise lead to the formation of bis-iodine by-products. Cyclizations involving terminal and substituted alkynes were performed. Further functionalizations demonstrated that the iodo derivatives obtained are potential synthetic intermediates that can increase the molecular complexity.
- Published
- 2011
40. Controlling Intracellular Macrocyclization for the Imaging of Protease Activity
- Author
-
Deju Ye, Jianghong Rao, Man Lung Ma, and Gaolin Liang
- Subjects
Protease ,Extramural ,medicine.medical_treatment ,Oxidation reduction ,General Chemistry ,Glutathione ,General Medicine ,Catalysis ,chemistry.chemical_compound ,chemistry ,Biochemistry ,Cell culture ,Cyclization ,Peptide Hydrolases ,Cell Line, Tumor ,medicine ,Humans ,Nanoparticles ,Oxidation-Reduction ,Intracellular - Published
- 2011
41. Cover Feature: Self-assembly of Fluorescent Dehydroberberine Enhances Mitochondria-Dependent Antitumor Efficacy (Chem. Eur. J. 39/2018)
- Author
-
Hong Liu, Runqi Yan, Ruibing An, Zhanni Gu, Deju Ye, Yuxuan Hu, and Haifeng Sun
- Subjects
Chemistry ,Feature (computer vision) ,Organic Chemistry ,Biophysics ,Cover (algebra) ,General Chemistry ,Self-assembly ,Mitochondrion ,Fluorescence ,Catalysis - Published
- 2018
42. Gold(I)-Catalyzed One-Pot Tandem Coupling/Cyclization: An Efficient Synthesis of Pyrrolo-/Pyrido[2,1-b]benzo[d][1,3]oxazin- 1-ones
- Author
-
Hong Liu, Guannan Liu, Yun Zhai, Xun Ji, Enguang Feng, Deju Ye, Hualiang Jiang, Yu Zhou, and Linxiang Zhao
- Subjects
Coupling ,Broad spectrum ,Tandem ,Chemistry ,General Chemistry ,Combinatorial chemistry ,D-1 ,Catalysis - Abstract
A highly efficient method has been developed for the one-pot synthesis of multi-ring heterocyclic compounds such as pyrrolo-/pyrido[2,1-b]benzo[d][1,3]oxazin-1-ones from o-aminobenzyl alcohols via a gold(I)-catalyzed tandem coupling/ cyclization reaction. Significantly, the strategy presents a straightforward and efficient approach to construct novel tricyclic or polycyclic molecular architectures in which two new C-N bonds and one C-O bond are formed in a one-pot reaction operation from two simple starting materials. Moreover, a broad spectrum of substrates can participate in the process effectively to produce the desired products in good yields.
- Published
- 2010
43. Gold- and Silver-Catalyzed Intramolecular Hydroamination of Terminal Alkynes: Water-Triggered Chemo- and Regioselective Synthesis of Fused Tricyclic Xanthines
- Author
-
Deju Ye, Hualiang Jiang, Yu Zhou, Xu Zhang, Dengyou Zhang, Hong Liu, Hengshuai Wang, and Lei Zhang
- Subjects
chemistry.chemical_classification ,chemistry ,Intramolecular force ,Microwave irradiation ,Regioselectivity ,Organic chemistry ,General Chemistry ,Hydroamination ,Combinatorial chemistry ,Tricyclic ,Biological evaluation ,Catalysis - Abstract
A simple, convenient and green synthetic approach to diverse fused tricyclic xanthines has been developed via gold(I) complex-catalyzed intramolecular hydroamination or silver(I)-catalyzed isomerization-hydroamination of terminal alkynes under microwave irradiation in water. The first synthesis of N9-annelated xanthines has also been reported.
- Published
- 2009
44. Silver-Catalyzed Intramolecular Cyclization ofo-(1-Alkynyl)benzamides: Efficient Synthesis of (1H)-Isochromen-1-imines
- Author
-
Xiao Ding, Hualiang Jiang, Yu Zhou, Hong Liu, Guannan Liu, Dengyou Zhang, and Deju Ye
- Subjects
chemistry.chemical_classification ,Isocoumarins ,Alkyne ,Regioselectivity ,General Chemistry ,Combinatorial chemistry ,Catalysis ,chemistry.chemical_compound ,chemistry ,Amide ,Intramolecular force ,Moiety ,Organic chemistry ,Hydroamination - Abstract
An efficient avenue for the facile and atom-economic synthesis of (1H)-isochromen-1- imines has been developed, and a broad spectrum of substrates can participate in the process effectively to produce the desired products in good yields. Significantly, this is the first report of the synthesis of (1H)-isochromen-1-imines that involves a silver(I)-catalyzed, regiocontrolled intramolecular addition of the carbonyl group of the amide moiety towards an alkyne.
- Published
- 2009
45. Fluorescent Coumarin-Artemisinin Conjugates as Mitochondria-Targeting Theranostic Probes for Enhanced Anticancer Activities
- Author
-
Xu Zhang, Diliang Guo, Hui Wang, Hong Liu, Zhanni Gu, Yu Zhou, Deju Ye, Qian Ba, and Yungen Xu
- Subjects
Theranostic Nanomedicine ,Apoptosis ,Mitochondrion ,Pharmacology ,Catalysis ,Drug Delivery Systems ,Coumarins ,Neoplasms ,medicine ,Humans ,Artemisinin ,Cytotoxicity ,Fluorescent Dyes ,Chemistry ,Organic Chemistry ,Cancer ,General Chemistry ,medicine.disease ,Artemisinins ,Cell biology ,Mitochondria ,Cancer cell ,Drug delivery ,Reactive Oxygen Species ,medicine.drug - Abstract
Mitochondria-targeting theranostic probes that enable the simultaneously reporting of and triggering of mitochondrial dysfunctions in cancer cells are highly attractive for cancer diagnosis and therapy. Three fluorescent mitochondria-targeting theranostic probes have been developed by linking a mitochondrial dye, coumarin-3-carboximide, with a widely used traditional Chinese medicine, artemisinin, to kill cancer cells. Fluorescence images showed that the designed coumarin-artemisinin conjugates localized mainly in mitochondria, leading to enhanced anticancer activities over artemisinin. High cytotoxicity against cancer cells correlated with the strong ability to accumulate in mitochondria, which could efficiently increase the intracellular reactive oxygen species level and induce cell apoptosis. This study highlights the potential of using mitochondria-targeting fluorophores to selectively trigger and directly visualize subcellular drug delivery in living cells.
- Published
- 2015
46. Cover Feature: Activatable Near-Infrared Probe for Fluorescence Imaging of γ-Glutamyl Transpeptidase in Tumor Cells and In Vivo (Chem. Eur. J. 59/2017)
- Author
-
Runqi Yan, Deju Ye, Liandong Feng, Jian He, Hong-Yuan Chen, Changge Ji, Zhengyang Zhou, Hua Shi, Zhiliang Luo, Guanfu Duan, and Ruibing An
- Subjects
Tumor imaging ,Fluorescence-lifetime imaging microscopy ,γ glutamyl transpeptidase ,Chemistry ,Organic Chemistry ,Near-infrared spectroscopy ,Tumor cells ,Nanotechnology ,General Chemistry ,Catalysis ,Feature (computer vision) ,In vivo ,Biophysics ,Cover (algebra) - Published
- 2017
47. Bioorthogonal cyclization-mediated in situ self-assembly of small-molecule probes for imaging caspase activity in vivo
- Author
-
Grigory Tikhomirov, Jianghong Rao, Adam J. Shuhendler, Deju Ye, Ling Tong, Dean W. Felsher, Sui Seng Tee, and Lina Cui
- Subjects
In situ ,General Chemical Engineering ,Image Processing ,Nanoparticle ,Nanotechnology ,Bioengineering ,Apoptosis ,Article ,Fluorescence ,Mice ,Experimental ,Computer-Assisted ,In vivo ,Neoplasms ,Image Processing, Computer-Assisted ,Animals ,Humans ,Cancer ,Fluorescent Dyes ,Caspase activity ,Microscopy ,Chemistry ,Organic Chemistry ,Neoplasms, Experimental ,General Chemistry ,Small molecule ,Xenograft Model Antitumor Assays ,3. Good health ,1.3 Chemical and physical sciences ,Microscopy, Fluorescence ,Cyclization ,Caspases ,Doxycycline ,Chemical Sciences ,Biophysics ,Nanoparticles ,Self-assembly ,Generic health relevance ,Bioorthogonal chemistry ,Biotechnology ,HeLa Cells - Abstract
Directed self-assembly of small molecules in living systems could enable a myriad of applications in biology and medicine, and already this has been used widely to synthesize supramolecules and nano/microstructures in solution and in living cells. However, controlling the self-assembly of synthetic small molecules in living animals is challenging because of the complex and dynamic in vivo physiological environment. Here we employ an optimized first-order bioorthogonal cyclization reaction to control the self-assembly of a fluorescent small molecule, and demonstrate its in vivo applicability by imaging caspase-3/7 activity in human tumour xenograft mouse models of chemotherapy. The fluorescent nanoparticles assembled in situ were imaged successfully in both apoptotic cells and tumour tissues using three-dimensional structured illumination microscopy. This strategy combines the advantages offered by small molecules with those of nanomaterials and should find widespread use for non-invasive imaging of enzyme activity in vivo.
- Published
- 2014
48. Caspase-responsive smart gadolinium-based contrast agent for magnetic resonance imaging of drug-induced apoptosis†
- Author
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Deju Ye, Sui Seng Tee, Prachi Pandit, Lina Cui, Jianghong Rao, Adam J. Shuhendler, Brian K. Rutt, Kimberly D. Brewer, and Grigory Tikhomirov
- Subjects
medicine.diagnostic_test ,biology ,business.industry ,Gadolinium ,chemistry.chemical_element ,Magnetic resonance imaging ,Bioengineering ,General Chemistry ,Fluorescence ,Article ,Text mining ,Nuclear magnetic resonance ,Rare Diseases ,chemistry ,In vivo ,Apoptosis ,Positron emission tomography ,Chemical Sciences ,medicine ,biology.protein ,Biomedical Imaging ,Nanotechnology ,business ,Caspase ,Cancer - Abstract
Non-invasive detection of caspase-3/7 activity in vivo has provided invaluable predictive information regarding tumor therapeutic efficacy and anti-tumor drug selection. Although a number of caspase-3/7 targeted fluorescence and positron emission tomography (PET) imaging probes have been developed, there is still a lack of gadolinium (Gd)-based magnetic resonance imaging (MRI) probes that enable high spatial resolution detection of caspase-3/7 activity in vivo. Here we employ a self-assembly approach and develop a caspase-3/7 activatable Gd-based MRI probe for monitoring tumor apoptosis in mice. Upon reduction and caspase-3/7 activation, the caspase-sensitive nano-aggregation MR probe (C-SNAM: 1) undergoes biocompatible intramolecular cyclization and subsequent self-assembly into Gd-nanoparticles (GdNPs). This results in enhanced r1 relaxivity—19.0 (post-activation) vs. 10.2 mM−1 s−1 (pre-activation) at 1 T in solution—and prolonged accumulation in chemotherapy-induced apoptotic cells and tumors that express active caspase-3/7. We demonstrate that C-SNAM reports caspase-3/7 activity by generating a significantly brighter T1-weighted MR signal compared to non-treated tumors following intravenous administration of C-SNAM, providing great potential for high-resolution imaging of tumor apoptosis in vivo.
- Published
- 2013
49. Positron emission tomography imaging of drug-induced tumor apoptosis with a caspase-triggered nanoaggregation probe
- Author
-
Jianghong Rao, Adam J. Shuhendler, Frederick T. Chin, Deju Ye, Bin Shen, Jongho Jeon, and Mikael Palner
- Subjects
Drug ,Diagnostic Imaging ,Fluorine Radioisotopes ,media_common.quotation_subject ,Analytical chemistry ,Caspase 3 ,Apoptosis ,Catalysis ,Article ,Mice ,Neoplasms ,Medical imaging ,medicine ,Animals ,Humans ,Benzothiazoles ,Caspase ,media_common ,medicine.diagnostic_test ,biology ,Molecular Structure ,Chemistry ,General Medicine ,General Chemistry ,Nanostructures ,Positron emission tomography ,Positron-Emission Tomography ,Cancer research ,biology.protein ,Heterografts ,Radiopharmaceuticals ,Oligopeptides ,HeLa Cells - Abstract
An 18F-labeled caspase-3 sensitive nano-aggregation PET tracer ([18F]CSNAT) was prepared and evaluated for imaging caspase-3 activity in doxorubicin-treated tumor xenografts. This enzyme-activatable PET tracer is designed to function in a novel mechanism – enhanced retention of the 18F activity in apoptotic tumors is achieved through intramolecular macrocyclization and in situ aggregation upon caspase-3 activation.
- Published
- 2013
50. Controlled self-assembling of gadolinium nanoparticles as smart molecular magnetic resonance imaging contrast agents
- Author
-
Jianghong Rao, Deju Ye, Gaolin Liang, John A. Ronald, Prachi Pandit, Yuanxin Chen, Man Lung Ma, and Brian K. Rutt
- Subjects
Microscopy, Confocal ,medicine.diagnostic_test ,Chemistry ,Extramural ,Gadolinium ,chemistry.chemical_element ,Nanoparticle ,Contrast Media ,Oxidation reduction ,Nanotechnology ,Magnetic resonance imaging ,General Medicine ,General Chemistry ,Magnetic Resonance Imaging ,Catalysis ,Article ,Cell Line, Tumor ,Self assembling ,medicine ,Magnetic nanoparticles ,Humans ,Magnetite Nanoparticles ,Oxidation-Reduction - Published
- 2010
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