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Many different types of nanoparticles have been suggested for tumor-targeted theranosis. However, most systems were prepared through a series of complicated processes and could not even overcome the blood–immune barriers. For the accurate diagnosis and effective treatment of cancers, herein we suggested the lipid micellar structure capturing quantum dot (QD) for cancer theranosis. The QD/lipid micelles (QDMs) were prepared using a simple self-assembly procedure and then conjugated with anti-epidermal growth factor receptor (EGFR) antibodies for tumor targeting. As a therapeutic agent, Bcl2 siRNA-cholesterol conjugates were loaded on the surface of QDMs. The EGFR-directed QDMs containing Bcl2 siRNA, so-called immuno-QDM/siBcl2 (iQDM/siBcl2), exhibited the more effective delivery of QDs and siBcl2 to target human colorectal cancer cells in cultures as well as in mouse xenografts. The effective in vivo targeting of iQDM/siBcl2 resulted in a more enhanced therapeutic efficacy of siBcl2 to the target cancer in mice. Based on the results, anti-EGFR QDM capturing therapeutic siRNA could be suggested as an alternative modality for tumor-targeted theranosis. [ABSTRACT FROM AUTHOR]

Many different types of nanoparticles have been suggested for tumor-targeted theranosis. However, most systems were prepared through a series of complicated processes and could not even overcome the blood–immune barriers. For the accurate diagnosis and effective treatment of cancers, herein we suggested the lipid micellar structure capturing quantum dot (QD) for cancer theranosis. The QD/lipid micelles (QDMs) were prepared using a simple self-assembly procedure and then conjugated with anti-epidermal growth factor receptor (EGFR) antibodies for tumor targeting. As a therapeutic agent, Bcl2 siRNA-cholesterol conjugates were loaded on the surface of QDMs. The EGFR-directed QDMs containing Bcl2 siRNA, so-called immuno-QDM/siBcl2 (iQDM/siBcl2), exhibited the more effective delivery of QDs and siBcl2 to target human colorectal cancer cells in cultures as well as in mouse xenografts. The effective in vivo targeting of iQDM/siBcl2 resulted in a more enhanced therapeutic efficacy of siBcl2 to the target cancer in mice. Based on the results, anti-EGFR QDM capturing therapeutic siRNA could be suggested as an alternative modality for tumor-targeted theranosis.

Currently, many challenges are associated with hepatocellular carcinoma (HCC) as the failure of early diagnosis, and the lack of effective therapy. This study aimed to investigate the possible role of tuftelin 1 (TUFT 1) in the early diagnosis of HCC and evaluate the potential contribution of the TUFT 1/Ca+2/phosphinositol 3 kinase (PI3K) pathway in dantrolene sodium (Dan) therapeutic outcomes. The study was performed on two sets of rats, the staging (30 rats) and treatment sets (80 rats). HCC was induced by a single dose of diethylnitrosamine (DENA). The hepatic content of TUFT 1 protein was assayed via western blot and immunohistochemistry (IHC), while PI3K, vascular endothelial growth factor (VEGF), Cyclin D1, and matrix‐metalloproteinase‐9 (MMP‐9) contents were assessed using enzyme‐linked immunosorbent assay. Hepatic and serum calcium were measured colorimetrically. Furthermore, the nuclear proliferation marker, (Ki‐67), (Kiel [Ki] where the antibody was produced in the University Department of Pathology and the original clone number is 67)—expression was assessed by IHC. TUFT 1/Ca+2/PI3K signaling pathway was progressively activated in the 3 studied stages of HCC with subsequent upregulation of angiogenesis, cell cycle, and metastasis. More interestingly, Dan led to TUFT 1/Ca+2/PI3K pathway disruption by diminution of the hepatic contents of TUFT 1, calcium, PI3K, VEGF, Cyclin D1, and MMP‐9 in a dose‐dependent pattern. TUFT 1 can serve as a theranostic biomarker in HCC. Moreover, Dan exerted an antineoplastic effect against HCC via the interruption of TUFT 1/Ca+2/PI3K pathway. Significance statement: We investigated the role of tuftelin 1 (TUFT 1) TUFT 1/Ca+2/phosphinositol 3 kinase (PI3K) pathway in giagnosis, staging and dantrolene sodium (Dan) therapy. Hepatocellular carcinoma (HCC) was induced by diethylnitrosamine (DENA). TUFT 1/Ca+2/PI3K signaling pathway was progressively activated during stages of HCC with upregulation of angiogenesis, cell cycle, and metastasis. Dan led to TUFT 1/Ca+2/PI3K pathway disruption by depressing the hepatic contents of TUFT 1, calcium, PI3K, vascular endothelial growth factor, Cyclin D1, and metalloproteinase 9 in a dose‐dependent pattern. TUFT 1 can serve as a theranostic biomarker in HCC and Dan showed a promising antineoplastic effect against HCC via the interruption of TUFT 1/Ca+2/PI3K pathway. [ABSTRACT FROM AUTHOR]

Global burden of cardiovascular diseases (CVDs) is one of the main and leading causes of death around the world. Atherosclerosis early detection still is the most impactful factor for controlling the spread of CVDs. Fight against CVDs requires the creation and development of new agents that can control and diminish these diseases. Gold nanoparticles (AuNPs) represent promising agents for future cardiovascular therapeutics. Synthesized and modified with unlimited modifiers, these nanoparticles can possess unique chemical, physical and biological properties and features that ensure clinical potentiality of AuNPs toward the cardiovascular system. In this review, we introduce most appropriate methods for the synthesis of gold nanoparticles as well as the related functionalization techniques. An important issue of the application of AuNPs in the cardiovascular theranosis is illustrated. Gold nanoparticles in conjugation with promising drugs will give double enhancement and ensure that most CVDs will be overcome. [ABSTRACT FROM AUTHOR]

Five different silica nanoparticles functionalized with vitamin B12, a derivative of coumarin found in green plants and a minimum content of an organotin(IV) fragment (1-MSN-Sn, 2-MSN-Sn, 2-SBA-Sn, 2-FSPm-Sn and 2-FSPs-Sn), were identified as excellent anticancer agents against triple negative breast cancer, one of the most diagnosed and aggressive cancerous tumors, with very poor prognosis. Notably, compound 2-MSN-Sn shows selectivity for cancer cells and excellent luminescent properties detectable by imaging techniques once internalized. The same compound is also able to interact with and nearly eradicate biofilms of Staphylococcus aureus, the most common bacteria isolated from chronic wounds and burns, whose treatment is a clinical challenge. 2-MSN-Sn is efficiently internalized by bacteria in a biofilm state and destroys the latter through reactive oxygen species (ROS) generation. Its internalization by bacteria was also efficiently monitored by fluorescence imaging. Since silica nanoparticles are particularly suitable for oral or topical administration, and considering both its anticancer and antibacterial activity, 2-MSN-Sn represents a new dual-condition theranostic agent, based primarily on natural products or their derivatives and with only a minimum amount of a novel metallodrug. [ABSTRACT FROM AUTHOR]

Nowadays, a number of promising strategies are being developed that aim at combining diagnostic and therapeutic capabilities into clinically effective formulations. Thus, the combination of a modified release provided by an organic encapsulation and the intrinsic physico-chemical properties from an inorganic counterpart opens new perspectives in biomedical applications. Herein, a biocompatible magnetic lipid nanocomposite vehicle was developed through an efficient, green and simple method to simultaneously incorporate magnetic nanoparticles and an anticancer drug (doxorubicin) into a natural nano-matrix. The theranostic performance of the final magnetic formulation was validated in vitro and in vivo, in melanoma tumors. The systemic administration of the proposed magnetic hybrid nanocomposite carrier enhanced anti-tumoral activity through a synergistic combination of magnetic hyperthermia effects and antimitotic therapy, together with MRI reporting capability. The application of an alternating magnetic field was found to play a dual role, (i) acting as an extra layer of control (remote, on-demand) over the chemotherapy release and (ii) inducing a local thermal ablation of tumor cells. This combination of chemotherapy with thermotherapy establishes a synergistic platform for the treatment of solid malignant tumors under lower drug dosing schemes, which may realize the dual goal of reduced systemic toxicity and enhanced anti-tumoral efficacy.

• Organometallic metal complexes have been utilized for biosensing and imaging. • There are also good examples of anticancer d6, d8 and d10 metal complexes. • Luminescent and anticancer metal complexes have been employed as theranostic agents. • Self-assembled metal complexes have good potentials for biomedical applications. • Chemical biology can facilitate biological studies of metal complexes. Organometallic d6, d8 and d10 metal complexes are known for their interesting photophysical and photochemical properties. This allows many of them to develop into luminescent probes for biosensing and imaging. In addition, some of the complexes have been found to show promising anticancer properties, with different molecular targets from the classical cisplatin and platinum-based chemotherapeutic agents, illustrating the possibility of using them to develop new therapy for cancers. Notably, there are examples of luminescent metal complexes showing good therapeutic values. They have been employed as theranostic agents which enable diagnosis and therapy simultaneously. This review highlights key features of organometallic d6, d8 and d10 metal complexes reported in the past 10 years and their applications in biosensing, imaging, cancer treatment and theranosis. We also discuss the limitations found in these complexes and provide insights into the future development of organometallic metal complexes for biomedical applications. [ABSTRACT FROM AUTHOR]

Nanoscale materials have demonstrated a very high potential in anticancer therapy by properly adjusting their functionalization and physicochemical properties. Herein, we report the synthesis of some novel vanadocene-loaded silica-based nanomaterials incorporating four different S-containing amino acids (penicillamine, methionine, captopril, and cysteine) and different fluorophores (rhodamine B, coumarin 343 or Alexa Fluor™ 647), which have been characterized by diverse solid-state spectroscopic techniques viz; FTIR, diffuse reflectance spectroscopies, 13 C and 51 V solid-state NMR spectroscopy, thermogravimetry and TEM. The analysis of the biological activity of the novel vanadocene-based nanostructured silicas showed that the materials containing cysteine and captopril aminoacids demonstrated high cytotoxicity and selectivity against triple negative breast cancer cells, making them very promising antineoplastic drug candidates. According to the biological results it seems that vanadium activity is connected to its incorporation through the amino acid, resulting in synergy that increases the cytotoxic activity against cancer cells of the studied materials presumably by increasing cell internalization. The results presented herein hold significant potential for future developments in mesoporous silica-supported metallodrugs, which exhibit strong cytotoxicity while maintaining low metal loading. They also show potential for theranostic applications highlighted by the analysis of the optical properties of the studied systems after incorporating rhodamine B, coumarin 343 (possible) in vitro anticancer analysis, or Alexa Fluor™ 647 ( in vivo studies of cancer models)., (© 2024 IOP Publishing Ltd.)

The one-pot cascade reaction of naturally occurring enzymes is exciting for highly selective complex reaction and biodegradable approaches. Tamoxifen is the main drug against breast cancer for decades and induces an anticancerous effect upon metabolic activation by cytochrome P450 (CYP450). Herein, bi-enzymatic nanoreactors (NRs) are developed as a multimodality platform for smart action against breast tumors. CYP BM3 of Bacillus magaterium (CYP) is co-confined with glucose oxidase (GOx) where GOx produces H 2 O 2 in the presence of glucose that elicits the CYP-mediated transformation of tamoxifen. The scintillating and mesoporous LaF 3 :Tb as nanocarrier showed advantages like a wide range of pore size and positive surface charge for efficient loading of enzyme couple, while the smallest pores were available for substrate/product diffusion. The obtained NRs were camouflaged with human serum albumin (HSA) to overcome premature enzyme leaching and provide active stealth properties. The nanocomposite was characterized for physicochemical properties and glucose-mediated sequential catalysis. The in vitro studies demonstrated the cell internalization of NRs in both ER+ and triple-negative breast cancer cell lines and showed significant cytotoxicity. The developed NRs not only improve the outcomes of endocrine therapy in ER+ cells but also synergistically act with oxidation therapy for enhanced therapeutic effect. Importantly, inhibition of triple-negative cells was also achieved. Thus, the development of the new multimodal nanomedicine of the present work should afford new tools towards the theranosis of breast cancer with minimized adverse effects. [ABSTRACT FROM AUTHOR]

Poly-l-lysine (PLL) nanoparticle (NP) system was prepared for the controlled release of curcumin (CUR) by pH stimuli, and its theranostic efficacy on cancer was compared to that of CUR solution in vitro and in vivo. Deoxycholic acid (DOCA), methoxy polyethylene glycol (MPEG) and cyanine 5.5 (cy5.5) were conjugated to the amine group of PLL through condensation reaction (PLL-DOCA-MPEG-cy5.5), followed by encapsulation of CUR by dialysis method (PLL-DOCA-MPEG-cy5.5/CUR NPs). The composition, morphology and size distribution of PLL-DOCA-MPEG-cy5.5 NPs were characterized by proton nuclear magnetic resonance (1H NMR), transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively. In vitro tests exhibited that changes in the charge and size of the NPs at low pH led to the improved cellular uptake of CUR into human hepatoma Hep3B cell line by electrostatically absorptive endocytosis. PEGylation with MPEG was turn out to be very effective to have a prolonged blood circulation time, in turn increased the EPR effect. In addition, the incorporation of Cy5.5 into NPs provided successful biodistribution images in vivo and ex vivo. Our findings suggest that PLL-DOCA-MPEG-cy5.5/CUR NPs may have promising applications in cancer theranosis.

Cancer is the second leading cause of death in the world, which is why it is so important to make an early and very precise diagnosis to obtain a good prognosis. Thanks to the combination of several imaging modalities in the form of the multimodal molecular imaging (MI) strategy, a great advance has been made in early diagnosis, in more targeted and personalized therapy, and in the prediction of the results that will be obtained once the anticancer treatment is applied. In this context, magnetic nanoparticles have been positioned as strong candidates for diagnostic agents as they provide very good imaging performance. Furthermore, thanks to their high versatility, when combined with other molecular agents (for example, fluorescent molecules or radioisotopes), they highlight the advantages of several imaging techniques at the same time. These hybrid nanosystems can be also used as multifunctional and/or theranostic systems as they can provide images of the tumor area while they administer drugs and act as therapeutic agents. Therefore, in this review, we selected and identified more than 160 recent articles and reviews and offer a broad overview of the most important concepts that support the synthesis and application of multifunctional magnetic nanoparticles as molecular agents in advanced cancer detection based on the multimodal molecular imaging approach.

Graphical abstract Highlights • Metal-Organic Frameworks (MOFs) as platform in of advanced combined therapy. • Biocompatibility is achieved by selecting non-toxic and/or endogenous building units. • Large porosity enables the co-encapsulation of multiple drugs in MOFs. • MOFs scaffolds can be used for theranosis, combining therapy and imaging. Abstract Different strategies have been developed to overcome limitations of traditional pharmacological treatments (biodegradation, low specificity, toxicity, side effects). Remarkably, the use of nanoplatforms as Drug Delivery Systems (DDS) to control the dose and the delivery kinetics of active ingredients (AIs) stands out as promising new generation of personalized therapies. Among other proposed materials, Metal-Organic Frameworks (MOFs) offer multiple versatilities for the accommodation of AIs: adaptable structure based on organic ligands and inorganic clusters as building units (BUs), that can be AIs themselves; accessible porosity and large surface areas; availability of functionalization sites; and biodegradability, among others. It is of great importance that MOFs, selected as bioplatforms, are biocompatible and do not exhibit toxicity. Even there are plenty of studies and reviews that explored the use of MOFs as DDS, they often include a single AI. In contrast, we wanted to focus on this review on MOF bioplatforms that exhibit advanced combined therapies. These advanced therapies could be achieved by: i) the co-encapsulation and simultaneous or sequential release of two or more AIs (e.g. drugs, metals, gases, biomolecules), ii) effective drug delivery at a target site after external triggered stimulus (near infrared-NIR, magnetic field), iii) monitoring administration towards a specific target (bioimaging), iv) combined AIs delivery and diagnosis (theranosis), and v) detection of different analytes (biosensors). All the promising combined advanced therapies based on MOFs bioplatforms herein reported open the path for the development of more efficient treatments. [ABSTRACT FROM AUTHOR]

Poly-L-lysine (PLL) nanoparticle (NP) system was prepared for the controlled release of curcumin (CUR) by pH stimuli, and its theranostic efficacy on cancer was compared to that of CUR solution in vitro and in vivo. Deoxycholic acid (DOCA), methoxy polyethylene glycol (MPEG) and cyanine 5.5 (cy5.5) were conjugated to the amine group of PLL through condensation reaction (PLL-DOCA-MPEG-cy5.5), followed by encapsulation of CUR by dialysis method (PLL-DOCA-MPEG-cy5.5/CUR NPs). The composition, morphology and size distribution of PLL-DOCA-MPEG-cy5.5 NPs were characterized by proton nuclear magnetic resonance (1H NMR), transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively. In vitro tests exhibited that changes in the charge and size of the NPs at low pH led to the improved cellular uptake of CUR into human hepatoma Hep3B cell line by electrostatically absorptive endocytosis. PEGylation with MPEG was turn out to be very effective to have a prolonged blood circulation time, in turn increased the EPR effect. In addition, the incorporation of Cy5.5 into NPs provided successful biodistribution images in vivo and ex vivo. Our findings suggest that PLL-DOCA-MPEG-cy5.5/CUR NPs may have promising applications in cancer theranosis. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA) is a rare disease with poor outcomes and limited research efforts into novel treatment options. A systematic review of CCA biomarkers was undertaken to identify promising biomarkers that may be used for theranosis (therapy and diagnosis). MEDLINE/EMBASE databases (1996–2019) were systematically searched using two strategies to identify biomarker studies of CCA. The PANTHER Go-Slim classification system and STRING network version 11.0 were used to interrogate the identified biomarkers. The TArget Selection Criteria for Theranosis (TASC-T) score was used to rank identified proteins as potential targetable biomarkers for theranosis. The following proteins scored the highest, CA9, CLDN18, TNC, MMP9, and EGFR, and they were evaluated in detail. None of these biomarkers had high sensitivity or specificity for CCA but have potential for theranosis. This review is unique in that it describes the process of selecting suitable markers for theranosis, which is also applicable to other diseases. This has highlighted existing validated markers of CCA that can be used for active tumor targeting for the future development of targeted theranostic delivery systems. It also emphasizes the relevance of bioinformatics in aiding the search for validated biomarkers that could be repurposed for theranosis.

Hyaluronic acid (HA) is a natural mucopolysaccharide and has many useful advantages, including biocompatibility, non-immunogenicity, chemical versatility, non-toxicity, biodegradability, and high hydrophilicity. Numerous tumor cells overexpress several receptors that have a high binding affinity for HA, while these receptors are poorly expressed in normal body cells. HA-based drug delivery carriers can offer improved solubility and stability of anticancer drugs in biological environments and allow for the targeting of cancer treatments. Based on these benefits, HA has been widely investigated as a promising material for developing the advanced clinical cancer therapies in various formulations, including nanoparticles, micelles, liposomes, and hydrogels, combined with other materials. We describe various approaches and findings showing the feasibility of improvement in theragnosis probes through the application of HA.

Nanoparticles (NPs) are small structures under 100 nm in dimension. Interrelationships among the morphological parameters and toxicity of NPs have been the focus of several investigations that assessed potential health risk in environmentally-exposed subjects and the realistic uses of NPs in medical practice. In the current review, we provide a summary of the cellular mechanisms of membrane-mediated transport, including old and novel molecules that transport nanostructures across cellular membranes. The effects of geochemical exposure to natural NPs are evaluated through epidemiological data and cancerous pathways activated by Fe2+ NPs. Specifically, we discuss screening for papillary thyroid carcinomas in the inhabitants of the Sicilian volcanic area surrounding Mount Etna to compare the incidence of thyroid carcinoma in this population. Lastly, considering the increased production of carbon nanotubes (CNTs), we examine the toxicity and potential use of these engineered NPs in drug delivery of an extensive amount of therapeutic and imaging molecules (theranosis) that can be conjugated to CNTs. [ABSTRACT FROM AUTHOR]

Nanotechnology plays an important role in the development of drug delivery, imaging, and diagnosis. In this study, nanocapsules containing protein-functionalized gold nanoclusters (AuNCs) as the shell and hydrophobic drug curcumin as the core were prepared as a tumor cell theranostic agent. After the nanocapsules were added into tumor cell media, they entered the cells with high efficiency and exhibited strong fluorescence within the cells. The results indicated that the nanocapsules were broken up in the cells and curcumin was released. Simultaneously, the nanocapsules exhibited significant inhibition effect against tumor cell proliferation in a concentration- and time-dependent manner, and the images of atomic force microscopy (AFM) showed that the cell morphology underwent obvious changes after the capsule treatment. Additionally, cell membrane appeared wrinkles after the cells treated with the nanocapsules, resulting in a rough cell surface, implying that the cytoskeleton would involve in the cell uptake of nanocapsules. Moreover, the AuNCs and curcumin in the system could exert synergistic effect on the inhibition of tumor cell growth and induction of cell apoptosis. The study highlights the potential of the system as a promising agent for drug delivery and tumor cell theranosis. [ABSTRACT FROM AUTHOR]

Abstract: The design of more efficient anticancer drugs requires a deeper understanding of their biodistribution and mechanism of action. Cell imaging agents could help to gain insight into biological processes and, consequently, the best strategy for attaining suitable scaffolds in which both biological and imaging properties are maximized. A new concept arises in this field that is the combination of two metal fragments as collaborative partners to provide the precise emissive properties to visualize the cell as well as the optimum cytotoxic activity to build more potent and selective chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Abstract: A mutifunctional ruthenium‐based conjugate Ru‐BSe was designed and synthesized. The Ru complex with favorable bioimaging function was covalently linked with a cancer‐targeted molecule that could be effectively internalized by the tumor to realize enhanced theranostic effects. The pH‐response of the Ru conjugate in tumor acidic microenvironment causes ligand substitution and release of therapeutic complex. This activated complex remains inert to the reducing biomolecule‐glutathione and terminally locates in mitochondria, in which it triggers oxidative stress, and activates intrinsic apoptosis. Real‐time monitoring reveals that this Ru conjugate could selectively accumulate in tumor tissue in vivo, which significantly suppresses tumor progression and alleviate the damage to normal organs, realizing the precise cancer theranosis. [ABSTRACT FROM AUTHOR]

In recent years, luminogens with the feature of aggregation-induced emission (AIEgen) have emerged as advanced luminescent materials for fluorescent nanomaterial preparation. AIEgen-based nanomaterials show enhanced fluorescence efficiency and superior photostability, which thusly offer unique advantages in biological applications. In this review, we will summarize the fabrication methods of AIEgen-based nanomaterials and their applications in in vitro/in vivo imaging, cell tracing, photodynamic therapy and drug delivery, focusing on the recent progress. [ABSTRACT FROM AUTHOR]

Introduction: Liquid biopsies (LB) are used routinely in clinical practice in two situations for late stage non-small-cell lung cancer (NSCLC) patients, (i) at the initial diagnosis when looking for activating mutations in EGFR in the absence of analyzable tissue DNA and, (ii) during tumor progression on a tyrosine kinase inhibitor treatment to look for the resistance mutation T790M in EGFR. LB is not presently recommended in daily practice for the diagnosis of NSCLC. Areas covered: We report the diagnosis of a NSCLC in a patient with bilateral ocular metastases after detection of a deletion in exon 19 of EGFR when using plasma DNA. Without histological analysis, the origin of the primary ocular metastasis was uncertain. In this context, a LB showing an activating mutation in EGFR and circulating tumor cells positive for TTF1 led to the diagnosis of NSCLC and targeted therapy. Expert commentary: When no tumor tissue sample is available a LB can be used to diagnose for metastatic NSCLC, when a mutation in EGFR is identified. While a tissue biopsy is the gold standard approach for the diagnosis of a NSCLC and for identification of activating mutations, LB can exceptionally provide both a diagnosis of the primitive tumor and indicate appropriate therapy based on a molecular analysis. [ABSTRACT FROM AUTHOR]

Iodide uptake across the membranes of thyroid follicular cells and cancer cells occurs through an active transport process mediated by the sodium-iodide symporter (NIS). The rat and human NIS-coding genes were cloned and identified in 1996. Evaluation of NIS gene and protein expression is critical for the management of thyroid cancer, and several approaches to increase NIS levels have been tried. Identification of the NIS gene has provided a means of expanding its role in radionuclide therapy and molecular target-specific theragnosis (therapy and diagnosis using the same molecular target). In this article, we describe the relationship between NIS expression and the thyroid carcinoma treatment using I-131 and alternative therapeutic approaches.

Bloodstream bacterial infections are a serious threat to global public health and economy. The recent figures released by National Center for Health Statistics indicate that more than a million Americans get affected by it each year and the sepsis mortality alone is about 28%-50% Hall et al. (2011). 1 Robust and affordable point-of-care medical technologies are, therefore, urgently needed for rapid decision-making to initiate appropriate line of treatment. Current techniques based on blood culture and serology do not have quick turnaround times or adequate sensitivities for early intervention. Moreover, antimicrobial resistance poses a great challenge in the fight towards effective bacterial infection management. Nanotheranostics is emerging as a novel strategy combining solutions for rapid diagnosis and treatment in a more personalized way. This review highlights the recent advances made in theranosis of bloodstream bacterial infections using different classes of nanomaterials and bioreceptors, and discusses present challenges and future way forward. [ABSTRACT FROM AUTHOR]

In recent years, luminogens with the feature of aggregation-induced emission (AIEgen) have emerged as advanced luminescent materials for fluorescent nanomaterial preparation. AIEgen-based nanomaterials show enhanced fluorescence efficiency and superior photostability, which thusly offer unique advantages in biological applications. In this review, we will summarize the fabrication methods of AIEgen-based nanomaterials and their applications in in vitro/in vivo imaging, cell tracing, photodynamic therapy and drug delivery, focusing on the recent progress.

Nano-sized systems have been used extensively for the delivery of various therapeutics, such as pharmaceuticals, proteins, and nucleic acids. Exosomes are small extracellular vesicles secreted from parent cells by fusion of multivesicular late endosomes with the plasma membrane, which act as an intercellular communication mediator and contain bioactive molecules. Thus, exosomes may possess potential as a natural delivery system. Polymersomes are synthetic vesicles composed of external bilayers, typically generated from amphiphilic block copolymers, which resemble many aspects of exosomes and have been utilized widely in many drug delivery applications. In this review, general properties of exosomes and polymersomes and their recent applications in the drug delivery areas and potential in theranostic approaches are discussed. [ABSTRACT FROM AUTHOR]

The work aimed at developing a novel MRI-based theranostic protocol for improving the anticancer efficacy of a Doxil-like liposomal formulation. The goal was achieved stimulating the intratumor release of the drug from the nanocarrier and favoring its diffusion in the lesion by the sequential application of low-intensity pulsed ultrasound. The protocol was tested on mice bearing a syngeneic breast cancer model. The combination of acoustic waves with different characteristics allowed for: i) the release of the drug and the co-encapsulated MRI agent (Gadoteridol) from the liposomes in the vessels of the tumor region, and ii) the extravasation of the released material, as well as intact liposomes, in the tumor stroma. The MR-T 1 contrast enhancement measured in the tumor reported on the delivery and US-triggered release of Doxorubicin. The developed protocol resulted in a marked increase in the intratumor drug concentration that, in turn, led to the complete regression of the lesion. The protocol has a good clinical translatability because all the components of the theranostic agent (Doxorubicin, liposomes, Gadoteridol) are approved for human use. [ABSTRACT FROM AUTHOR]

The article focuses on study on role of Magnetic resonance imaging (MRI) contrast agents in pharmacological studies and offers information on classification of MRI contrast agents which includes T¹ agents, Chemical Exchange Saturation Transfer (CEST) agents and hyperpolarized probes.

Theranostic delivery systems are nanostructures that combine the modality of therapy and diagnostic imaging. Polymeric micro- and nanobubbles, spherical vesicles containing a gas core, have been proposed as new theranostic carriers for MRI-guided therapy. In this study, chitosan nanobubbles were purposely tuned for the co-delivery of prednisolone phosphate and a Gd(III) complex, as therapeutic and MRI diagnostic agent, respectively. Perfluoropentane was used for filling up the internal core of the formulation. These theranostic nanobubbles showed diameters of about 500 nm and a positive surface charge that allows the interaction with the negatively charged Gd-DOTP complex. Pluronic F68 was added to the nanobubble aqueous suspension as stabilizer agent. The encapsulation efficiency was good for both the active compounds, and a prolonged drug release profile was observed in vitro . The effect of ultrasound stimulation on prednisolone phosphate release was evaluated at 37 °C. A marked increase on drug release kinetics with no burst effect was obtained after the exposure of the system to ultrasound. Furthermore, the relaxivity of the MRI probe changed upon incorporation in the nanobubble shell, thereby offering interesting opportunity in dual MRI-US experiments. The ultrasound characterization showed a good in vitro echogenicity of the theranostic nanobubbles. In summary, chitosan drug-loaded nanobubbles with Gd(III) complex bound to their shell might be considered a new platform for imaging and drug delivery with the potential of improving anti-cancer treatments. [ABSTRACT FROM AUTHOR]

The low specificity and high risk of intracranial hemorrhage associated with currently approved thrombolytic therapies limit their efficacy in recanalizing occluded vessels. Here, a nanoscale thrombolytic agent is demonstrated by immobilizing tissue plasminogen activator molecules (tPA) over 20 nm clustered iron oxide nanocubes (NCs). The resulting nanoconstructs (tPA-NCs) are capable of dissolving clots via both direct interaction of tPA with the fibrin network (chemical lysis) and localized hyperthermia upon stimulation of superparamagnetic NCs with alternating magnetic fields (AMFs) (mechanical lysis). In vitro, as compared to free tPA, the proposed nanoconstructs demonstrate a ≈100-fold increase in dissolution rate, possibly because of a more intimate interaction of tPA with the fibrin network. The clot dissolution rate is further enhanced (≈10-fold) by mild, localized heating resulting from the exposure of tPA-NCs to AMF. Intravital microscopy experiments demonstrate blood vessel reperfusion within a few minutes post tail vein injection of tPA-NCs. The proposed nanoconstructs also exhibit high transverse relaxivity (>400 × 10-3 m−1 s−1) for magnetic resonance imaging. The multifunctional properties and the 3 orders of magnitude enhancement in clot dissolution make tPA-NCs a promising nano-theranosis agent in thrombotic disease. [ABSTRACT FROM AUTHOR]

Abstract: Targeting tissues/cells using probing materials to detect diseases such as cancer and inflammatory disease has been attempted with some success. Most of the molecular targets used in diagnosis and therapy were identified through the discovery of intracellular signaling pathways. Among intracellular signaling processes, the ubiquitination of proteins, and thereby their proteasomal degradation, is important because it plays a role in most diseases involving alterations to a component of the ubiquitination system, particularly E3 ligases, which have selective target-binding affinity and are key to the success of regulating the disorder. The regulation and monitoring of E3 ligases can be achieved using peptides containing protein–protein binding motifs. We generated a human protein-derived peptide that could target Smurf1, a member of the E3 ligase family, by competitively binding to osteo-Smads. To effectively deliver it into cells, the peptide was further modified with a cell-penetrating peptide. The peptide contains two fluorescent dyes: fluorescein isothiocyanate (FITC; absorbance/emission wavelengths: 495/519 nm) as a fluorophore and black hole quencher-1 (BHQ-1) as a fluorescence quencher. When the target Smurf1 combined with complementary sequences in the peptide probe, the distance between the fluorophore and BHQ-1 increased via a conformational change, resulting in the recovery of the fluorescence signal. Simultaneously, the degradation of Smad1/5/8 was blocked by the binding of the peptide probe to Smurf1, leading to the potentiation of the osteogenic pathway, which was reflected by an increase in the expression of osteoinductive genes, such as alkaline phosphatase and osteocalcin. Possible future applications of the peptide probe include its integration into imaging tools for the diagnosis of Smurf1-overexpressing diseases. [Copyright &y& Elsevier]

The work aimed at developing a MRI-guided protocol for the visualization of the release of material entrapped in liposomes stimulated by the local application of pulsed low-intensity non-focused ultrasound (pLINFU). The task was achieved by formulating liposomes filled up with the clinically approved paramagnetic agent gadoteridol, because the release of the agent from the nanovesicles is accompanied by a significant MRI signal enhancement. The protocol was validated in vivo on mice-bearing subcutaneous syngeneic B16 melanoma and i.v. injected with the paramagnetic liposomes. Upon exposing tumor to pLINFU (3MHz, insonation time 2min, duty cycle 50%) few minutes after liposomes injection, a signal enhancement of ca. 35% was detected. The effective release of the agent was confirmed by the strong enhancement measured in kidneys calyx and bladder due to the rapid renal excretion of the agent released in the tumor. [ABSTRACT FROM AUTHOR]

Abstract: A novel dual functional theranosis platform is developed based on manganese magnetism-engineered iron oxide (MnMEIO) and gold nanorods (AuNRs) to combine magnetic resonance (MR) imaging and photothermal therapy in one nanocluster. The platform showed improved T 2 -weighted MR imaging and exhibited a near-infrared (NIR) induced temperature elevation due to the unique characteristics of AuNRs@MnMEIOs nanoclusters. The obtained dual functional spherical-shaped nanoclusters showed low cytotoxicity, and high cellular uptake efficiency. The AuNRs@MnMEIOs nanoclusters also demonstrated a 1.9 and 2.2 folds r 2 relaxivity value higher than those of monodispersed MnMEIO and Resovist. In addition, in vivo MR imaging study found that the contrast enhancements were – 70.4 ± 4.3% versus – 7.5 ± 3.0% in Her-2/neu overexpression tumors as compared to the control tumors. More importantly, NIR laser irradiation to the tumor site resulted in outstanding photothermal therapeutic efficacy and without damage to the surrounding tissue. In additional, the prepared dual functional AuNRs@MnMEIOs display high stability and furthermore disperse even in the presence of external magnet, showing that AuNRs@MnMEIOs nanoclusters can be manipulated by an external magnetic field. Therefore, such nanoclusters combined MR imaging and photothermal therapeutic functionality can be developed as a promising nanosystem for effective cancer diagnosis and therapy. [Copyright &y& Elsevier]

Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis in an infarcted myocardium. The purpose of the current investigation was to validate whether a radiolabeled VEGF delivery system can be effectively monitored in vivo, and to ascertain whether the growth factor induces an angiogenic effect to facilitate recovery from infarct conditions in rodent myocardial infarction (MI) models. Rat MI models were divided into three groups, one with left anterior descending coronary artery (LAD) ligation with no injection (the control group), one with LAD ligation and I-131 VEGF injection (the VEGF group), and one with LAD ligation and I-131 VEGF-loaded chitosan injection (the VIC group). On day 7 after injection, autoradiography imaging was performed, followed by semiquantitative and histopathologic analyses. In semi-quantitative analysis, the mean anterior-to-inferior wall ratio of the VIC group was significantly higher than those of the control and VEGF groups ( p<0.05). Histopathologic experiments revealed a marked increase in microvascular density in the VIC group compared to those of the control and VEGF groups ( p<0.05). Intramyocardially injected VIC was not only effectively monitored in vivo, but also stimulated therapeutic angiogenesis in the infarcted myocardium. Our findings support that the developed VIC is a novel theranostic tool to improve myocardial perfusion following myocardial infarction. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Cancer is the second leading cause of death in the world, which is why it is so important to make an early and very precise diagnosis to obtain a good prognosis. Thanks to the combination of several imaging modalities in the form of the multimodal molecular imaging (MI) strategy, a great advance has been made in early diagnosis, in more targeted and personalized therapy, and in the prediction of the results that will be obtained once the anticancer treatment is applied. In this context, magnetic nanoparticles have been positioned as strong candidates for diagnostic agents as they provide very good imaging performance. Furthermore, thanks to their high versatility, when combined with other molecular agents (for example, fluorescent molecules or radioisotopes), they highlight the advantages of several imaging techniques at the same time. These hybrid nanosystems can be also used as multifunctional and/or theranostic systems as they can provide images of the tumor area while they administer drugs and act as therapeutic agents. Therefore, in this review, we selected and identified more than 160 recent articles and reviews and offer a broad overview of the most important concepts that support the synthesis and application of multifunctional magnetic nanoparticles as molecular agents in advanced cancer detection based on the multimodal molecular imaging approach. [ABSTRACT FROM AUTHOR]