Department of Breast Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou 450003, Henan, China; Henan Provincial Engineering Research Center of Breast Cancer Precise Prevention and Treatment, Zhengzhou 450003, Henan, China.
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
Nanomedicine. 2023 Feb;48:102630. doi: 10.1016/j.nano.2022.102630. Epub 2022 Nov 23.
The hypoxic microenvironment of breast cancer substantially reduces oxygen-dependent free radical generation. Overexpression of glutathione (GSH) in tumor cells mitigates the impact of free radical generation. In this study, we designed and developed an oxygen-independent alkyl radical nanogenerator (copper monosulfide/2,2'-azabis(2-imidazoline) dihydrochloride@bovine serum albumin; CuS/AIPH@BSA) with spatiotemporally controlled properties and GSH consumption to enhance breast cancer therapy. We encapsulated the alkyl radical initiator, AIPH, in hollow mesoporous CuS nanoparticles with photothermal conversion effect and enveloped them in BSA. AIPH was released and decomposed to generate alkyl radicals in hypoxic breast cancer with the photothermal conversion effect of CuS under near-infrared laser irradiation. CuS consumed high GSH levels in tumor cells because it could form complex with GSH and thereby enhanced free radical treatment. In vivo and in vitro assays demonstrated the anti-tumor efficacy of the rationally designed free-radical nanogenerator in hypoxic microenvironment of breast cancer without showing systemic toxicity.
乳腺癌的缺氧微环境大大降低了氧依赖性自由基的生成。肿瘤细胞中超表达谷胱甘肽（GSH）可以减轻自由基生成的影响。在这项研究中，我们设计并开发了一种具有时空可控特性和 GSH 消耗的氧非依赖性烷基自由基纳米发生器（硫化铜/2,2'-双（2-咪唑啉）二盐酸盐@牛血清白蛋白；CuS/AIPH@BSA），以增强乳腺癌治疗效果。我们将烷基自由基引发剂 AIPH 封装在具有光热转换效应的中空介孔 CuS 纳米粒子中，并将其包裹在 BSA 中。在近红外激光照射下，CuS 的光热转换效应使 AIPH 在缺氧乳腺癌中释放并分解，产生烷基自由基。由于 CuS 可以与 GSH 形成复合物，从而消耗肿瘤细胞中的高 GSH 水平，增强了自由基的治疗效果。体内和体外实验证明了这种合理设计的自由基纳米发生器在乳腺癌缺氧微环境中的抗肿瘤功效，同时没有表现出系统毒性。
