Sun Rui, Liu Xiaocen, Li Guangzhi, Wang Hui, Luo Yongxiang, Huang Guixiao, Wang Xisheng, Zeng Guohua, Liu Zhuang, Wu Song
Institute of Urology, The Affiliated Luohu Hospital of Shenzhen University, Shenzhen 518000, China.
Liaoning Key Laboratory of Proteomics, Dalian Medical University, Dalian 116044, China.
ACS Nano. 2020 Jul 28;14(7):8135-8148. doi: 10.1021/acsnano.0c01300. Epub 2020 Jun 29.
Hydrogen gas can mitigate oxidative stress in many diseases and is regarded to be safe and free of side effects. Inspired by a metalloenzyme in a variety of microorganisms, here, we propose a photoactivated H nanogenerator that comprises a fluorinated chitosan (FCS), a chemotherapeutic drug (gemcitabine, GEM), and a catalyst of H production ([FeFe]TPP) that can form self-assembled [FeFe]TPP/GEM/FCS nanoparticles (NPs). The [FeFe]TPP/GEM/FCS NPs exhibit excellent transmucosal and tumor cell penetration capacities after intravesical instillation into the bladder and can efficiently produce H gas upon 660 nm laser irradiation, which significantly enhances the efficacy of hydrogen chemotherapy of cancer and . Moreover, we discover that H gas in hydrogen chemotherapy can inhibit mitochondrial function, hinder ATP synthesis, and cause a reduction of the P-gp efflux pump function, which finally attenuates P-gp protein drug transport capacity in cancer cells. This photoactivated H evolution to improve the therapeutic efficacy of chemotherapy of bladder cancer may present an effective hydrogen chemotherapy strategy for cancer treatment.
氢气可以减轻多种疾病中的氧化应激，并且被认为是安全且无副作用的。受多种微生物中金属酶的启发，在此，我们提出了一种光活化氢纳米发生器，它由氟化壳聚糖（FCS）、一种化疗药物（吉西他滨，GEM）和一种产氢催化剂（[FeFe]TPP）组成，它们可以形成自组装的[FeFe]TPP/GEM/FCS纳米颗粒（NPs）。将[FeFe]TPP/GEM/FCS NPs经膀胱内灌注到膀胱后，表现出优异的经黏膜和肿瘤细胞穿透能力，并且在660 nm激光照射下能够高效产氢，这显著提高了癌症氢化疗的疗效。此外，我们发现氢化疗中的氢气可以抑制线粒体功能，阻碍ATP合成，并导致P-糖蛋白外排泵功能降低，最终减弱癌细胞中P-糖蛋白的药物转运能力。这种通过光活化产氢来提高膀胱癌化疗疗效的方法可能为癌症治疗提供一种有效的氢化疗策略。
