A new G-quadruplex-specific photosensitizer inducing genome instability in cancer cells by triggering oxidative DNA damage and impeding replication fork progression DOI Creative Commons
Marco Deiana, José María Andrés Castán, Pierre Josse

и другие.

Nucleic Acids Research, Год журнала: 2023, Номер 51(12), С. 6264 - 6285

Опубликована: Май 16, 2023

Abstract Photodynamic therapy (PDT) ideally relies on the administration, selective accumulation and photoactivation of a photosensitizer (PS) into diseased tissues. In this context, we report new heavy-atom-free fluorescent G-quadruplex (G4) DNA-binding PS, named DBI. We reveal by fluorescence microscopy that DBI preferentially localizes in intraluminal vesicles (ILVs), precursors exosomes, which are key components cancer cell proliferation. Moreover, purified exosomal DNA was recognized G4-specific antibody, thus highlighting presence such G4-forming sequences vesicles. Despite absence signal from nuclei, light-irradiated DBI-treated cells generated reactive oxygen species (ROS), triggering 3-fold increase nuclear G4 foci, slowing fork progression elevated levels both base damage, 8-oxoguanine, double-stranded breaks. Consequently, found to exert significant phototoxic effects (at nanomolar scale) toward lines tumor organoids. Furthermore, vivo testing reveals induces not only formation damage but also apoptosis zebrafish, specifically area where had accumulated. Collectively, approach shows promise for image-guided PDT.

Язык: Английский

Clinical Development of Metal Complexes as Photosensitizers for Photodynamic Therapy of Cancer DOI
Johannes Karges

Angewandte Chemie International Edition, Год журнала: 2021, Номер 61(5)

Опубликована: Ноя. 8, 2021

Cancer has emerged over the last decades as one of deadliest diseases in world. Among most commonly used techniques (i.e. surgery, immunotherapy, radiotherapy or chemotherapy), increasing attention been devoted towards photodynamic therapy. However, vast majority clinically applied photosensitizers are not ideal and associated with several limitations including poor aqueous solubility, photostability slow clearance from body, causing photosensitivity. In an effort to overcome these drawbacks, much incorporation a metal ion. Herein, clinical development metal-containing compounds Purlytin

Язык: Английский

Процитировано

305
The design of small-molecule prodrugs and activatable phototherapeutics for cancer therapy DOI Creative Commons
Hai‐Hao Han, Han-Min Wang, Paramesh Jangili

и другие.

Chemical Society Reviews, Год журнала: 2023, Номер 52(3), С. 879 - 920

Опубликована: Янв. 1, 2023

This tutorial review provides a general overview for the design of prodrugs and activatable phototherapeutics which enables development improved therapies.

Язык: Английский

Процитировано

153
BODIPY as a Multifunctional Theranostic Reagent in Biomedicine: Self‐Assembly, Properties, and Applications DOI
Hong‐Bo Cheng,

Xiaoqiao Cao,

Shuchun Zhang

и другие.

Advanced Materials, Год журнала: 2022, Номер 35(18)

Опубликована: Ноя. 18, 2022

Abstract The use of boron dipyrromethene (BODIPY) in biomedicine is reviewed. To open, its synthesis and regulatory strategies are summarized, inspiring cutting‐edge work post‐functionalization highlighted. A brief overview assembly model BODIPY then provided: introduced as a promising building block for the formation single‐ multicomponent self‐assembled systems, including nanostructures suitable aqueous environments, thereby showing great development potential supramolecular applications. frontier progress biomedical application thereafter described, supported by examples frontiers applications BODIPY‐containing smart materials: it mainly involves materials based on blocks their assemblies fluorescence bioimaging, photoacoustic imaging, disease treatment photodynamic therapy, photothermal immunotherapy. Lastly, not only current status family field but also challenges worth considering summarized. At same time, insights into future prospects biomedically applicable provided.

Язык: Английский

Процитировано

139
Integration of TADF Photosensitizer as “Electron Pump” and BSA as “Electron Reservoir” for Boosting Type I Photodynamic Therapy DOI
Wenlong Chen,

Zehui Wang,

Mingyu Tian

и другие.

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(14), С. 8130 - 8140

Опубликована: Март 31, 2023

Type I photosensitization provides an effective solution to the problem of unsatisfactory photodynamic therapeutic (PDT) effects caused by tumor hypoxia. The challenge in development mode is boost photosensitizer's own electron transfer capacity. Herein, we found that use bovine serum albumin (BSA) encapsulate a thermally activated delayed fluorescence (TADF) photosensitizer PS can significantly promote PDT process generate mass superoxide anions (O2•–). This opened new strategy employing BSA as "electron reservoir" and TADF pump". We integrated these roles one system preparing nanophotosensitizer PS@BSA. performance was demonstrated with cells under hypoxic conditions. Furthermore, PS@BSA took full advantage tumor-targeting role achieved efficient for tumor-bearing mice vivo experiments. work route improve efficiency tumors.

Язык: Английский

Процитировано

131
A Dual‐Locked Activatable Phototheranostic Probe for Biomarker‐Regulated Photodynamic and Photothermal Cancer Therapy DOI
Xin Wei, Chi Zhang, Shasha He

и другие.

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(26)

Опубликована: Апрель 9, 2022

Activatable phototheranostics holds promise for precision cancer treatment owing to the "turn-on" signals and therapeutic effects. However, most activatable phototheranostic probes only possess photodynamic therapy (PDT) or photothermal (PTT), which suffer from poor efficacy due deficient cellular oxygen complex tumor microenvironment. We herein report a dual-locked probe that activates near-infrared fluorescence (NIRF) in tumor, triggers PDT response tumor-periphery biomarker, switches PTT upon detecting tumor-core-hypoxia biomarker. This PDT-PTT auto-regulated exhibits complete ablation under photoirradiation of single laser source by producing cytotoxic singlet at periphery generating hyperthermia tumor-core where is too hypoxic PDT. represents promising molecular design approach toward precise phototheranostics.

Язык: Английский

Процитировано

124
Rational Design in Photopharmacology with Molecular Photoswitches DOI Creative Commons
Piermichele Kobauri, Frank J. Dekker, Wiktor Szymański

и другие.

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(30)

Опубликована: Апрель 7, 2023

Photopharmacology is an attractive approach for achieving targeted drug action with the use of light. In photopharmacology, molecular photoswitches are introduced into structure biologically active small molecules to allow optical control their potency. Going beyond trial and error, photopharmacology has progressively applied rational design methodologies devise light-controlled bioactive ligands. this review, we categorize photopharmacological efforts from standpoint medicinal chemistry strategies, focusing on diffusible photochromic ligands modified that operate through E-Z bond isomerization. vast majority cases, photoswitchable designed as analogs existing compounds, a variety approaches. By analyzing in detail comprehensive list instructive examples, describe state art discuss future opportunities photopharmacology.

Язык: Английский

Процитировано

104
Triggered azobenzene-based prodrugs and drug delivery systems DOI
Jundong Zhu, Tao Guo, Zheng Wang

и другие.

Journal of Controlled Release, Год журнала: 2022, Номер 345, С. 475 - 493

Опубликована: Март 23, 2022

Язык: Английский

Процитировано

85
meso-Methyl BODIPY Photocages: Mechanisms, Photochemical Properties, and Applications DOI
Pradeep Shrestha, Dnyaneshwar Kand, Roy Weinstain

и другие.

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(32), С. 17497 - 17514

Опубликована: Авг. 3, 2023

meso-methyl BODIPY photocages have recently emerged as an exciting new class of photoremovable protecting groups (PPGs) that release leaving upon absorption visible to near-infrared light. In this Perspective, we summarize the development these PPGs and highlight their critical photochemical properties applications. We discuss PPGs, structure–photoreactivity studies, insights into photoreaction mechanism, scope functional can be caged, chemical synthesis structures, how substituents alter water solubility PPG direct specific subcellular compartments. Applications exploit unique optical are also discussed, from wavelength-selective photoactivation biological studies photoresponsive organic materials photomedicine.

Язык: Английский

Процитировано

59
A Near‐Infrared Light‐Activated Photocage Based on a Ruthenium Complex for Cancer Phototherapy DOI
Guangli He, Maomao He, Ran Wang

и другие.

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(24)

Опубликована: Март 9, 2023

Conventional photocages only respond to short wavelength light, which is a significant obstacle developing efficient phototherapy in vivo. The development of activated by near-infrared (NIR) light at wavelengths from 700 950 nm important for vivo studies but remains challenging. Herein, we describe the synthesis photocage based on ruthenium (Ru) complex with NIR light-triggered photocleavage reaction. commercial anticancer drug, tetrahydrocurcumin (THC), was coordinated RuII center create Ru-based that readily responsive 760 nm. inherited properties THC. As proof-of-concept, further engineered self-assembled photocage-based nanoparticle system amphiphilic block copolymers. Upon exposure nm, Ru complex-based were released polymeric nanoparticles and efficiently inhibited tumor proliferation

Язык: Английский

Процитировано

57
Architecture of Vanadium‐Based MXene Dysregulating Tumor Redox Homeostasis for Amplified Nanozyme Catalytic/Photothermal Therapy DOI
Ruoxi Zhao, Yanlin Zhu, Lili Feng

и другие.

Advanced Materials, Год журнала: 2023, Номер 36(2)

Опубликована: Сен. 21, 2023

Abstract Taking the significance of special microenvironment for tumor cell survival into account, disrupting redox homeostasis is highly prospective improving therapeutic efficacy. Herein, a multifunctional 2D vanadium‐based MXene nanoplatform, V 4 C 3 /atovaquone@bovine albumin (V /ATO@BSA, abbreviated as VAB) has been elaborately constructed ATO‐enhanced nanozyme catalytic/photothermal therapy. The within cells eventually disrupted, showing remarkable anti‐tumor effect. VAB nanoplatform with mixed vanadium valence states can induce cascade catalyzed reactions in microenvironment, generating plenty reactive oxygen species (ROS) effective glutathione consumption to amplify oxidative stress. Meanwhile, stable and strong photothermal effect under near‐infrared irradiation not only causes necrosis cells, but also improves its peroxidase‐like activity. In addition, release ATO effectively alleviate endogenous limit triphosadenine formation inhibit mitochondrial respiration. As result, expression heat shock proteins suppressed overcome thermoresistance production ROS be further promoted due injury. Moreover, presents high photoacoustic imaging performances. brief, provide therapy broadening biomedical applications MXene.

Язык: Английский

Процитировано

51