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Journal of the American Chemical Society Nov 2023Ruthenium(II) polypyridyl complexes form a vast family of molecules characterized by their finely tuned photochemical and photophysical properties. Their ability to... (Review)
Review
Ruthenium(II) polypyridyl complexes form a vast family of molecules characterized by their finely tuned photochemical and photophysical properties. Their ability to undergo excited-state deactivation via photosubstitution reactions makes them quite unique in inorganic photochemistry. As a consequence, they have been used, in general, for building dynamic molecular systems responsive to light but, more particularly, in the field of oncology, as prodrugs for a new cancer treatment modality called photoactivated chemotherapy (PACT). Indeed, the ability of a coordination bond to be selectively broken under visible light irradiation offers fascinating perspectives in oncology: it is possible to make poorly toxic agents in the dark that become activated toward cancer cell killing by simple visible light irradiation of the compound inside a tumor. In this Perspective, we review the most important concepts behind the PACT idea, the relationship between ruthenium compounds used for PACT and those used for a related phototherapeutic approach called photodynamic therapy (PDT), and we discuss important questions about real-life applications of PACT in the clinic. We conclude this Perspective with important challenges in the field and an outlook.
Topics: Humans; Ruthenium; Coordination Complexes; Photochemotherapy; Light; Neoplasms; Antineoplastic Agents; Photosensitizing Agents
PubMed: 37846939
DOI: 10.1021/jacs.3c01135 -
Cells Nov 2023Phototherapy, encompassing the utilization of both natural and artificial light, has emerged as a dependable and non-invasive strategy for addressing a diverse range of... (Review)
Review
Phototherapy, encompassing the utilization of both natural and artificial light, has emerged as a dependable and non-invasive strategy for addressing a diverse range of illnesses, diseases, and infections. This therapeutic approach, primarily known for its efficacy in treating skin infections, such as herpes and acne lesions, involves the synergistic use of specific light wavelengths and photosensitizers, like methylene blue. Photodynamic therapy, as it is termed, relies on the generation of antimicrobial reactive oxygen species (ROS) through the interaction between light and externally applied photosensitizers. Recent research, however, has highlighted the intrinsic antimicrobial properties of light itself, marking a paradigm shift in focus from exogenous agents to the inherent photosensitivity of molecules found naturally within pathogens. Chemical analyses have identified specific organic molecular structures and systems, including protoporphyrins and conjugated C=C bonds, as pivotal components in molecular photosensitivity. Given the prevalence of these systems in organic life forms, there is an urgent need to investigate the potential impact of phototherapy on individual molecules expressed within pathogens and discern their contributions to the antimicrobial effects of light. This review delves into the recently unveiled key molecular targets of phototherapy, offering insights into their potential downstream implications and therapeutic applications. By shedding light on these fundamental molecular mechanisms, we aim to advance our understanding of phototherapy's broader therapeutic potential and contribute to the development of innovative treatments for a wide array of microbial infections and diseases.
Topics: Humans; Photosensitizing Agents; Phototherapy; Photochemotherapy; Anti-Infective Agents; Acne Vulgaris
PubMed: 37998399
DOI: 10.3390/cells12222664 -
Photochemistry and Photobiology 2023
Topics: Photosensitizing Agents; Aminolevulinic Acid; Photochemotherapy
PubMed: 37997489
DOI: 10.1111/php.13852 -
The Ocular Surface Oct 2023Induced corneal collagen crosslinking and mechanical stiffening via ultraviolet-A photoactivation of riboflavin (UVA CXL) is now a common treatment for corneal ectasia... (Review)
Review
Induced corneal collagen crosslinking and mechanical stiffening via ultraviolet-A photoactivation of riboflavin (UVA CXL) is now a common treatment for corneal ectasia and Keratoconus. Some effects of the procedure such as induced mechanical stiffening, corneal flattening, and cellular toxicity are well-known, but others remain more controversial. Authors report a variety of contradictory effects, and provide evidence based on individual results and observations. A full understanding of the effects of and mechanisms behind this procedure are essential to predicting its outcome. A growing interest in modifications to the standard UVA CXL protocol, such as transepithelial or accelerated UVA CXL, makes analyzing the literature as a whole more urgent. This review presents an analysis of both the agreed-upon and contradictory results reported and the various methods used to obtain them.
Topics: Humans; Cornea; Ultraviolet Rays; Collagen; Riboflavin; Keratoconus; Cross-Linking Reagents; Photosensitizing Agents; Corneal Stroma
PubMed: 37683969
DOI: 10.1016/j.jtos.2023.09.003 -
Advanced Healthcare Materials Sep 2023Owing to their long absorption wavelengths, high molar absorptivity, and tunable photosensitivity, phthalocyanines have been widely used in photodynamic therapy (PDT).... (Review)
Review
Owing to their long absorption wavelengths, high molar absorptivity, and tunable photosensitivity, phthalocyanines have been widely used in photodynamic therapy (PDT). However, phthalocyanines still face the drawbacks of poor targeting, "always-on" photosensitizing properties, and unsatisfactory therapeutic efficiency, which limit their wide applications in biomedical fields. Thus, new design strategies such as modification of targeting molecules, formation of nanoparticles, and activating photosensitizers are developed to improve the above defects. Notably, recent studies have shown that novel phthalocyanines are not only used in fluorescence imaging and PDT, but also in photoacoustic imaging, photothermal imaging, sonodynamic therapy, and photothermal therapy. This review focuses on recent design strategies, applications in biomedicine, and clinical development of phthalocyanines, providing ideas and references for the design and application of phthalocyanine, so as to promote their future transformation into clinical applications.
Topics: Photochemotherapy; Photosensitizing Agents; Isoindoles; Chemical Phenomena
PubMed: 37039069
DOI: 10.1002/adhm.202300263 -
Chemical Reviews Aug 2023Over the last few decades, various forms of regulated cell death (RCD) have been discovered and were found to improve cancer treatment. Although there are several... (Review)
Review
Over the last few decades, various forms of regulated cell death (RCD) have been discovered and were found to improve cancer treatment. Although there are several reviews on RCD induced by photodynamic therapy (PDT), a comprehensive summary covering metal-based photosensitizers (PSs) as RCD inducers has not yet been presented. In this review, we systematically summarize the works on metal-based PSs that induce different types of RCD, including ferroptosis, immunogenic cell death (ICD), and pyroptosis. The characteristics and mechanisms of each RCD are explained. At the end of each section, a summary of the reported commonalities between different metal-based PSs inducing the same RCD is emphasized, and future perspectives on metal-based PSs inducing novel forms of RCD are discussed at the end of the review. Considering the essential roles of metal-based PSs and RCD in cancer therapy, we hope that this review will provide the stage for future advances in metal-based PSs as RCD inducers.
Topics: Humans; Photosensitizing Agents; Regulated Cell Death; Photochemotherapy; Metals; Neoplasms
PubMed: 37534710
DOI: 10.1021/acs.chemrev.3c00161 -
Nature Communications Sep 2023Phototherapy of deep tumors still suffers from many obstacles, such as limited near-infrared (NIR) tissue penetration depth and low accumulation efficiency within the...
Phototherapy of deep tumors still suffers from many obstacles, such as limited near-infrared (NIR) tissue penetration depth and low accumulation efficiency within the target sites. Herein, stimuli-sensitive tumor-targeted photodynamic nanoparticles (STPNs) with persistent luminescence for the treatment of deep tumors are reported. Purpurin 18 (Pu18), a porphyrin derivative, is utilized as a photosensitizer to produce persistent luminescence in STPNs, while lanthanide-doped upconversion nanoparticles (UCNPs) exhibit bioimaging properties and possess high photostability that can enhance photosensitizer efficacy. STPNs are initially stimulated by NIR irradiation before intravenous administration and accumulate at the tumor site to enter the cells through the HER2 receptor. Due to Pu18 afterglow luminescence properties, STPNs can continuously generate ROS to inhibit NFκB nuclear translocation, leading to tumor cell apoptosis. Moreover, STPNs can be used for diagnostic purposes through MRI and intraoperative NIR navigation. STPNs exceptional antitumor properties combined the advantages of UCNPs and persistent luminescence, representing a promising phototherapeutic strategy for deep tumors.
Topics: Humans; Gallbladder Neoplasms; Photosensitizing Agents; Luminescence; Carcinoma in Situ; Photochemotherapy; Nanoparticles
PubMed: 37709778
DOI: 10.1038/s41467-023-41389-1 -
Small (Weinheim An Der Bergstrasse,... Jul 2023Anticancer immunotherapy is hampered by the poor tumor immunogenicity and immunosuppressive tumor microenvironment (TME). Herein, a liposome nanodrug co-encapsulating...
Anticancer immunotherapy is hampered by the poor tumor immunogenicity and immunosuppressive tumor microenvironment (TME). Herein, a liposome nanodrug co-encapsulating doxycycline hydrochloride (Doxy) and chlorin e6 (Ce6) to simultaneously induce autophagy inhibition and mitochondria dysfunction for potentiating tumor photo-immunotherapy is developed. Under near infrared laser irradiation, Ce6 generates cytotoxic reactive oxygen species (ROS) and elicits robust photodynamic therapy (PDT)-induced immunogenic cell death (ICD) for immunosuppressive TME remodeling. In addition, Doxy induced mitochondria dysfunction, which increases ROS generation and enhances PDT to exert more potent killing effect and more powerful ICD. Meanwhile, Doxy increases MHC-I expression on tumor cells surface by efficient autophagy inhibition, leading to more efficient antigen presentation and CTLs recognition to increase tumor immunogenicity. The nanodrugs elicit remarkable antitumor therapy by combining Ce6-mediated PDT and Doxy-induced autophagy inhibition and mitochondria dysfunction. The developed nanodrugs represent a highly efficient strategy for improving cancer immunotherapy.
Topics: Photosensitizing Agents; Photochemotherapy; Reactive Oxygen Species; Immunotherapy; Nanoparticles; Autophagy; Cell Line, Tumor; Porphyrins; Tumor Microenvironment
PubMed: 37060227
DOI: 10.1002/smll.202300280 -
Nature Communications Nov 2023Multidrug-resistant (MDR) bacteria cause severe clinical infections and a high mortality rate of over 40% in patients with immunodeficiencies. Therefore, more effective,...
Multidrug-resistant (MDR) bacteria cause severe clinical infections and a high mortality rate of over 40% in patients with immunodeficiencies. Therefore, more effective, broad-spectrum, and accurate treatment for severe cases of infection is urgently needed. Here, we present an adoptive transfer of macrophages loaded with a near-infrared photosensitizer (Lyso700D) in lysosomes to boost innate immunity and capture and eliminate bacteria through a photodynamic effect. In this design, the macrophages can track and capture bacteria into the lysosomes through innate immunity, thereby delivering the photosensitizer to the bacteria within a single lysosome, maximizing the photodynamic effect and minimizing the side effects. Our results demonstrate that this therapeutic strategy eliminated MDR Staphylococcus aureus (MRSA) and Acinetobacter baumannii (AB) efficiently and cured infected mice in both two models with 100% survival compared to 10% in the control groups. Promisingly, in a rat model of central nervous system bacterial infection, we performed the therapy using bone marrow-divided macrophages and implanted glass fiber to conduct light irradiation through the lumbar cistern. 100% of infected rats survived while none of the control group survived. Our work proposes an efaficient and safe strategy to cure MDR bacterial infections, which may benefit the future clinical treatment of infection.
Topics: Humans; Rats; Mice; Animals; Photosensitizing Agents; Photochemotherapy; Staphylococcal Infections; Staphylococcus aureus; Bacteria; Macrophages; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Methicillin-Resistant Staphylococcus aureus; Acinetobacter baumannii
PubMed: 37945555
DOI: 10.1038/s41467-023-43074-9 -
Cells Sep 2023Immunosuppressants are emerging as promising candidates for cancer therapy with lower cytotoxicity compared to traditional chemotherapy drugs; yet, the intrinsic side...
Immunosuppressants are emerging as promising candidates for cancer therapy with lower cytotoxicity compared to traditional chemotherapy drugs; yet, the intrinsic side effects such as immunosuppression remain a critical concern. Herein, we introduce a photoactivatable antitumor immunosuppressant called dmBODIPY-FTY720 (BF) that shows no cytotoxicity but can be temporally and locally activated by deep-red light illumination to induce tumor cell apoptosis. To further reduce potential side effects, we integrate BF with another classic photosensitizer called methylene blue (MB) that is activated under the same wavelength of deep-red light (>650 nm) and successfully establish a red-light-activatable AND Boolean logic gate through a mechanism that we found to be synergetic apoptotic induction. At further decreased dosages, deep-red light illumination does not induce cell death in the presence of either BF or MB, but significant cancer cell death is triggered in the presence of both drugs. Therefore, the dosage of BF is further reduced, which will be highly beneficial to minimize any potential side effects of BF. This AND-gated strategy has been successfully applied in vivo for effective suppression of hepatocarcinoma tumors in living mice.
Topics: Mice; Animals; Photochemotherapy; Cell Line, Tumor; Immunosuppressive Agents; Light; Photosensitizing Agents
PubMed: 37830565
DOI: 10.3390/cells12192351