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用于癌症治疗中产生过氧亚硝酸盐的光可裂解可见光触发蒽醌衍生水溶性嵌段共聚物

Photocleavable Visible Light-Triggered Anthraquinone-Derived Water-Soluble Block Copolymer for Peroxynitrite Generation in Cancer Therapy.

作者信息

Paul Soumya, Ghosh Shilpendu, Maity Tanmoy, Behera Priyanka Priyadarshini, Mukherjee Arindam, De Priyadarsi

出版信息

ACS Macro Lett. 2024 Mar 19;13(3):288-295. doi: 10.1021/acsmacrolett.3c00728. Epub 2024 Feb 18.

Abstract

We report a facile stimuli-responsive strategy to generate reactive oxygen and nitrogen species (ROS and RNS) in the biological milieu from a photocleavable water-soluble block copolymer under visible light irradiation (427 nm, 2.25 mW/cm). An anthraquinone-based water-soluble polymeric nitric oxide (NO) donor () is synthesized, which exhibits NO release in the range of 40-65 μM within 10 h of photoirradiation with a half-life of 30-103 min. Additionally, produces peroxynitrite (ONOO) and singlet oxygen (O) under photoirradiation. To understand the mechanism of NO release and photolysis of the functional group under blue light, we prepared a small-molecule anthraquinone-based -nitrosamine (). The cellular investigation of the effect of spatiotemporally controlled ONOO and O generation from the NO donor polymeric nanoparticles in a triple negative breast adenocarcinoma (MDA-MB-231) under visible light irradiation (white light, 5.83 mW/cm; total dose 31.5 J/cm) showed an IC of 0.6 mg/mL. The stimuli-responsive strategy using a photolabile water-soluble block copolymer employed to generate ROS and RNS in a biological setting widens the horizon for their potential in cancer therapy.

摘要

我们报道了一种简便的刺激响应策略,即在可见光照射(427 nm,2.25 mW/cm²)下,由可光裂解的水溶性嵌段共聚物在生物环境中产生活性氧和氮物种(ROS和RNS)。合成了一种基于蒽醌的水溶性聚合物一氧化氮(NO)供体(),在光照射10小时内,其NO释放量在40 - 65 μM范围内,半衰期为30 - 103分钟。此外,在光照射下会产生过氧亚硝酸盐(ONOO⁻)和单线态氧(¹O₂)。为了理解蓝光下NO释放和官能团光解的机制,我们制备了一种基于蒽醌的小分子亚硝基胺()。对在可见光照射(白光,5.83 mW/cm²;总剂量31.5 J/cm²)下,由NO供体聚合物纳米颗粒在三阴性乳腺腺癌(MDA - MB - 231)中时空控制产生的ONOO⁻和¹O₂的细胞效应研究表明,其半数抑制浓度(IC)为0.6 mg/mL。使用光不稳定水溶性嵌段共聚物在生物环境中产生ROS和RNS的刺激响应策略拓宽了它们在癌症治疗中潜力的视野。

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