A Bioactive Photosensitizer for Hypoxia‐Tolerant Molecular Targeting‐Photo‐Immunotherapy of Malignant Tumor

Advanced Functional Materials, Год журнала: 2023, Номер 34(12)

Опубликована: Дек. 15, 2023

Abstract Photosensitizers (PSs) with effective reactive oxygen species generation ability against hypoxia are of great potential for clinical treatment malignant tumors. However, complex tumor microenvironment, such as antioxidative responses and immunosuppression, would ineluctably limit the efficiency photodynamic therapy (PDT). Herein, a molecular‐targeting photosensitizer QTANHOH is rationally designed histone deacetylases (HDACs‐targeting photo‐immunotherapy application. The PS displays excellent type‐I/II PDT performance, exhibiting significant phototoxicity toward cancer cells half maximal inhibitory concentration (IC 50 ) less than 10 n m in both normoxia conditions under blue laser irradiation. Moreover, bioactive compound could inhibit HDACs activate immune microenvironment to boost efficacy on immunocompetent BALB/c mice breast cancer, leading eradication solid inhibition metastasis. Notably, introduces an alternative strategy achieve superior phototherapy therapy.

Язык: Английский

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Iridium(III)-Based Infrared Two-Photon Photosensitizers: Systematic Regulation of Their Photodynamic Therapy Efficacy

Inorganic Chemistry, Год журнала: 2023, Номер 62(39), С. 16122 - 16130

Опубликована: Сен. 17, 2023

Cyclometalated iridium(III) complexes are of significant importance in the field antitumor photodynamic therapy (PDT), whether they exist as single molecules or incorporated into nanomaterials. Nevertheless, a comprehensive examination relationship between their molecular structure and PDT effectiveness remains awaited. The influencing factors two-photon excited can be anticipated to further multiplied, particularly relation intricate nonlinear optical properties. At present, body research on this topic is lacking, few discernible patterns have been identified. In study, through systematic regulation, nitro-substituted styryl group 1-phenylisoquinoline ligand containing YQ2 was found most potent infrared excitable photosensitizer 4 × 3 combination library cyclometalated Ir(III) complexes. could enter cells via an energy-dependent caveolae-mediated pathway, bind specifically mitochondria, produce 1O2 response 808 nm LPL irradiation, activate caspases, induce apoptosis. vitro, displayed remarkable phototherapy index for both malignant melanoma (>885) non-small-cell lung cancer (>1234) based these functions minimally deleterious human normal liver kidney cells. vivo phototherapy, inhibited tumor growth by impressive 85% eliminated from bodies mice with half-life short 43 h. This study has potential contribute significantly development phototherapeutic drugs that extremely effective treating large, profoundly located solid tumors well understanding structure-activity Ir(III)-based PSs PDT.

Язык: Английский

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A 700 nm LED Light Activated Ru(II) Complex Destroys Tumor Cytoskeleton via Photosensitization and Photocatalysis

Advanced Healthcare Materials, Год журнала: 2024, Номер unknown

Опубликована: Апрель 18, 2024

Abstract Photoactivable chemotherapy (PACT) using metallic complexes provides spatiotemporal selectivity over drug activation for targeted anticancer therapy. However, the poor absorption in near‐infrared (NIR) light region of most renders tissue penetration challenging. Herein, an NIR triggered dinuclear photoactivable Ru(II) complex ( Ru2 ) is presented and antitumor mechanism comprehensively investigated. The introduction a donor–acceptor–donor (D–A–D) linker greatly enhances intramolecular charge transition, resulting high molar extinction coefficient with extended triplet excited state lifetime. Most importantly, when activated by 700 nm light, exhibits unique slow photodissociation kinetics that facilitates synergistic photosensitization photocatalytic activity to destroy diverse intracellular biomolecules. In vitro vivo experiments show nanomolar photocytotoxicity toward 4T1 cancer cells via induction calcium overload endoplasmic reticulum (ER) stress. These findings provide robust foundation development NIR‐activated PACT phototherapeutic application.

Язык: Английский

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Photoactivatable Ruthenium Complexes Containing Minimal Straining Benzothiazolyl-1,2,3-triazole Chelators for Cancer Treatment

Inorganic Chemistry, Год журнала: 2024, Номер 63(14), С. 6202 - 6216

Опубликована: Фев. 22, 2024

Ruthenium(II) complexes containing diimine ligands have contributed to the development of agents for photoactivated chemotherapy. Several approaches been used obtain photolabile Ru(II) complexes. The two most explored use monodentate and incorporation steric effects between bidentate Ru(II). However, introduction electronic in has less explored. Herein, we report a systematic experimental, theoretical, photocytotoxicity study novel series Ru1–Ru5 general formula [Ru(phen)2(N∧N′)]2+, where N∧N′ are different minimal strained based on 1-aryl-4-benzothiazolyl-1,2,3-triazole (BTAT) scaffold, being CH3 (Ru1), F (Ru2), CF3 (Ru3), NO2 (Ru4), N(CH3)2 (Ru5) substituents R4 phenyl ring. stable solution dark, but upon irradiation water with blue light (λex = 465 nm, 4 mW/cm2) photoejection ligand BTAT was observed by HPLC-MS spectrometry UV–vis spectroscopy, t1/2 ranging from 4.5 14.15 min depending properties corresponding BTAT, Ru4 (the one more electron withdrawing substituent, NO2). ground state singlet excited triplet using density functional theory (DFT) time-dependent DFT (TD-DFT) calculations. A mechanism Ru complexes, H2O, is proposed. Phototoxicity studies A375 HeLa human cancer cell lines showed that new were strongly phototoxic. An enhancement emission intensity cells treated Ru5 response increasing doses due ligand. These suggest could serve as photocleavable protecting group cytotoxic bis-aqua ruthenium warhead [Ru(phen)2(OH2)2]2+.

Язык: Английский

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Sulphur- and Selenium-for-Oxygen Replacement as a Strategy to Obtain Dual Type I/Type II Photosensitizers for Photodynamic Therapy

Molecules, Год журнала: 2023, Номер 28(7), С. 3153 - 3153

Опубликована: Апрель 1, 2023

The effect on the photophysical properties of sulfur- and selenium-for-oxygen replacement in skeleton oxo-4-dimethylaminonaphthalimide molecule (DMNP) has been explored at density functional (DFT) level theory. Structural parameters, excitation energies, singlet-triplet energy gaps (ΔES-T), spin-orbit coupling constants (SOC) have computed. determined SOCs indicate an enhanced probability intersystem crossing (ISC) both thio- seleno-derivatives (SDMNP SeDMNP, respectively) and, consequently, enhancement singlet oxygen quantum yields. Inspection Type I reactions reveals that electron transfer mechanisms leading to generation superoxide is feasible for all compounds, suggesting a dual I/Type II activity.

Язык: Английский

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