Journal of Controlled Release ( IF 10.8 ) Pub Date : 2020-03-05 , DOI: 10.1016/j.jconrel.2020.03.007 Peijing An 1 , Fengying Fan 2 , Dihai Gu 1 , Zhiguo Gao 1 , Abul Monsur Showkot Hossain 3 , Baiwang Sun 1
Tumor microenvironment (TME)-responsive nanoformulations that catalyze a cascade of intracellular redox reactions showed promise for tumor treatment with high specificity and efficiency. In this study, we report Cu2+-doped zeolitic imidazolate frameworks-coated polydopamine nanoparticles (PDA@Cu/ZIF-8 NPs) for glutathione-triggered and photothermal-reinforced sequential catalytic therapy against breast cancer. In the TME, the PDA@Cu/ZIF-8 NPs could initially react with antioxidant glutathione (GSH), inducing GSH depletion and Cu+ generation. Whereafter, the generated Cu+ would catalyze local H2O2 to produce highly toxic hydroxyl radicals (·OH) through an efficient Fenton-like reaction even in weakly acidity. Importantly, the PDA could exert excellent photothermal conversion effect to simultaneously accelerate GSH consumption and improve the Fenton-like reaction for further expanding the intracellular oxidative stress, which innovatively achieves a synergistic photothermal-chemodynamic therapy for highly efficient anticancer treatment.
中文翻译:
光热增强和谷胱甘肽触发的原位级联纳米催化治疗。
肿瘤微环境(TME)响应的纳米制剂,催化细胞内氧化还原反应的级联显示出有望以高特异性和高效率进行肿瘤治疗。在这项研究中,我们报告了铜2 +掺杂的沸石咪唑酸盐骨架涂层的聚多巴胺纳米颗粒(PDA @ Cu / ZIF-8 NPs)用于谷胱甘肽触发和光热增强的顺序催化治疗乳腺癌。在TME中,PDA @ Cu / ZIF-8 NP最初可以与抗氧化剂谷胱甘肽(GSH)反应,诱导GSH消耗和Cu +生成。此后,生成的Cu +将催化局部H 2 O 2甚至在弱酸度下也能通过有效的类似于Fenton的反应生成剧毒的羟基自由基(·OH)。重要的是,PDA可以发挥出色的光热转化作用,同时加速GSH的消耗并改善Fenton样反应,进一步扩大细胞内的氧化应激,从而创新地实现了用于高效抗癌治疗的协同光热化学动力疗法。