Phototherapy, including photodynamic therapy and photothermal therapy, has the potential to treat several types of cancer.
Theranostic systems are receiving ever-increasing attention due to their potential therapeutic utility, imaging enhancement capability, and promise for advancing the field of personalized medicine, particularly as it relates to the diagnosis, staging, and treatment of cancer. In this Tutorial Review, we provide an introduction to the concepts of theranostic drug delivery effected via use of conjugates that are able to target cancer cells selectively, provide cytotoxic chemotherapeutics, and produce readily monitored imaging signals in vitro and in vivo. The underlying design concepts, requiring the synthesis of conjugates composed of imaging reporters, masked chemotherapeutic drugs, cleavable linkers, and cancer targeting ligands, are discussed. Particular emphasis is placed on highlighting the potential benefits of fluorogenic reaction-based targeted systems that are activated for both imaging and therapy by cellular entities, e.g., thiols, reactive oxygen species and enzymes, which are present at relatively elevated levels in tumour environments, physiological characteristics of cancer, e.g., hypoxia and acidic pH. Also discussed are systems activated by an external stimulus, such as light. The work summarized in this Tutorial Review will help define the role fluorogenic reaction-based, cancer-targeting theranostics may have in advancing drug discovery efforts, as well as improving our understanding of cellular uptake and drug release mechanisms.
Activatable (turn‐on) probes that permit the rapid, sensitive, selective, and accurate identification of cancer‐associated biomarkers can help drive advances in cancer research. Herein, a NAD(P)H:quinone oxidoreductase‐1 (NQO1)‐specific chemiluminescent probe 1 is reported that allows the differentiation between cancer subtypes. Probe 1 incorporates an NQO1‐specific trimethyl‐locked quinone trigger moiety covalently tethered to a phenoxy‐dioxetane moiety through a para‐aminobenzyl alcohol linker. Bio‐reduction of the quinone to the corresponding hydroquinone results in a chemiluminescent signal. As inferred from a combination of in vitro cell culture analyses and in vivo mice studies, the probe is safe, cell permeable, and capable of producing a “turn‐on” luminescence response in an NQO1‐positive A549 lung cancer model. On this basis, probe 1 can be used to identify cancerous cells and tissues characterized by elevated NQO1 levels.
This tutorial review highlights the potential of nanoscale porous organic polymers in diagnosis and therapy of different types of cancers.
Both chronic and acute neurodegenerative diseases have been associated with high morbidity and mortality, along with the death of neurons in different areas of the brain, and there are few or no effective curative therapy options for treatment of patients. [3,4] These disorders are a major cause of concern for the health and quality of life in the aging society, since age is the greatest risk factor for neurodegenerative disease. [5] The World Health Organization has predicted that in next 20 years neurodegenerative disease will become the second most common cause of mortality after cardiovascular disease. [6] Neurodegenerative processes begin long before their clinical symptoms are evident, and evolve for years slowly and irreversibly. Hence, there is an urgent need to diagnose neurodegenerative disease as early as possible and to distinguish between different neurodegenerative disorders with shared and unique symptoms to facilitate decision making regarding choice of treatment. Timely diagnosis is important for the adoption of therapeutic modalities in clinical trials prior to moderate dementia exhibition, to appraise and apply antidotes to maximally preserve the cognitive functions or to slow down the course of these disorders. The ability to analyze and identify risk factors for cognitive deficit would represent an extraordinary advancement in the field of dementia. [5] The main modern diagnostic technologies for the early examination of neurodegenerative disease pathology, neuroimaging techniques, include radioligandsbased positron emission tomography (PET), 3D single-photon emission-computed tomography (SPECT), and structural magnetic resonance imaging (MRI). Although PET and SPECT are the most used imaging techniques for neurodegenerative diseases, their application is limited by high cost, involvement of hazardous radiolabeled compounds, need for sophisticated instruments, and application of complex data acquisition and analysis protocols. The MRI technique has relatively low spatial resolution as well as intrinsically poor sensitivity to distinguish morphological differences between disease biomarkers and the surrounding tissue. Recently, fluorescence diagnosis technology has become an attractive and potential alternative to diagnose and probe the progression of neurodegenerative diseases, because of being rapid, noninvasive, sensitive, simple, real-time, low-cost, and high-resolution in nature. [7] There are several uses for Neurodegenerative diseases are debilitating disorders that feature progressive and selective loss of function or structure of anatomically or physiologically associated neuronal systems. Both chronic and acute neurodegenerative diseases are associated with high morbidity and mortality along with the death of neurons in different areas of the brain; moreover, there are few or no effective curative therapy options for treating these disorders. There is an urgent need to diagnose neurodegenerative disease as early as possible, and to distinguish between different disorders with overlap...
This review highlights pnictogen-based therapeutic agents, from ancient clinical drugs to recently emerging layered photonic nanomedicines. In addition, an update on recent biosafety studies of layered pnictogen is also provided.
Sonodynamic therapy (SDT) has garnered extensive attention as a noninvasive treatment for deep tumors. Furthermore, imiquimod (R837), an FDA-approved toll-like receptor 7 agonist, is commonly used in clinical settings as an immune adjuvant. We prepared an activatable sonodynamic sensitizer platform (MR) based on glutathione-sensitive disulfide bonds linking Leu-MB, the reduced form of methylene blue (MB), and R837 to achieve efficient combinatory SDT and immunotherapy for tumors without harming normal tissues. We also used the amphiphilic polymer C18PMH-PEG to create self-assembled MB-R837-PEG (MRP) nanoparticles for immunosonodynamic therapy (iSDT). iSDT is a cancer treatment that combines activatable SDT and immunotherapy. Our iSDT demonstrated an excellent sonodynamic effect only at the tumor site, demonstrating high specificity in killing tumor cells when compared to SDT reported in the literature. The iSDT improves its tumor-killing effect by inducing an immune response, which is accomplished by secreted immune adjuvants in the tumor site. MRP was selectively activated by glutathione in the tumor microenvironment to release MB and R837, exhibiting excellent antitumor sonodynamic and immune responses. In addition, when combined with an α-PD-L1 antibody for immune checkpoint blockade, this therapy effectively inhibited tumor metastasis. Furthermore, mice treated with iSDT and α-PD-L1 antibody did not develop tumors even after tumor reinoculation, indicating that long-term immune memory was achieved. The concept of sonodynamic sensitizer preparation as a next-generation iSDT based on a noninvasive synergistic therapeutic modality applicable in the near future is presented in this study.
Elucidating the underlying photochemical mechanisms of action (MoA) of photodynamic therapy (PDT) may allow its efficacy to be improved and could set the stage for the development of new classes of PDT photosensitizers. Here, we provide evidence that “photoredox catalysis in cells,” wherein key electron transport pathways are disrupted, could constitute a general MoA associated with PDT. Taking the cellular electron donor nicotinamide adenine dinucleotide as an example, we have found that well-known photosensitizers, such as Rose Bengal, BODIPY, phenoselenazinium, phthalocyanine, and porphyrin derivatives, are able to catalyze its conversion to NAD + . This MoA stands in contrast to conventional type I and type II photoactivation mechanisms involving electron and energy transfer, respectively. A newly designed molecular targeting photocatalyst (termed CatER) was designed to test the utility of this mechanism-based approach to photosensitizer development. Photoexcitation of CatER induces cell pyroptosis via the caspase 3/GSDME pathway. Specific epidermal growth factor receptor positive cancer cell recognition, high signal-to-background ratio tumor imaging (SBRTI = 12.2), and good tumor growth inhibition (TGI = 77.1%) are all hallmarks of CatER. CatER thus constitutes an effective near-infrared pyroptotic cell death photo-inducer. We believe the present results will provide the foundation for the synthesis of yet-improved phototherapeutic agents that incorporate photocatalytic chemistry into their molecular design.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.