Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung 804201, Taiwan.
Department of Chemical Engineering and Biotechnology and Graduate Institute of Biochemical and Biomedical Engineering, National Taipei University of Technology, Taipei 106344, Taiwan.
ACS Appl Bio Mater. 2021 Oct 18;4(10):7485-7496. doi: 10.1021/acsabm.1c00741. Epub 2021 Oct 7.
Photothermal therapy (PTT) is a potential treatment for cancer that makes use of near-infrared (NIR) laser irradiation and is expected to assist traditional anti-cancer drug therapies; however, the therapeutic efficacy of PTT is restricted by thermal resistance due to the overexpression of heat shock proteins and insufficient penetration depth of lasers. Thus, PTT needs to be combined with additional therapeutic methods to obtain the optimal therapeutic efficacy for cancer. Herein, a multifunctional therapeutic platform combining PTT with glucose-triggered chemodynamic therapy (CDT) and glutathione (GSH)-triggered hypoxia relief was developed via GOx@MBSA-PPy-MnO NPs (GOx for glucose oxidase, M for FeO, BSA for bovine serum albumin, and PPy for polypyrrole). GOx@MBSA-PPy-MnO NPs have excellent photothermal efficiency and can release Mn, which catalyzes the transformation of HO into hydroxyl radicals (·OH) and O via a Fenton-like reaction, effectively destroying cancer cells and relieving tumor hypoxia. Meanwhile, a high content of HO was produced via GOx catalysis of glucose, further enhancing the CDT efficiency. In addition, and experiments showed that the inhibition of cancer cell proliferation and effective inhibition of tumors could be caused by the combined PTT/glucose-triggered CDT effects and hypoxia relief of the GOx@MBSA-PPy-MnO NPs. Overall, this work provides evidence of a synergistic therapy that remarkably improves therapeutic efficacy and significantly prolongs the lifetime of mice compared with controls.
光热疗法（PTT）是一种利用近红外（NIR）激光照射的癌症潜在治疗方法，有望辅助传统抗癌药物疗法；然而，由于热休克蛋白的过度表达和激光的穿透深度不足，PTT 的治疗效果受到热阻力的限制。因此，PTT 需要与其他治疗方法结合使用，以获得癌症的最佳治疗效果。在此，通过 GOx@MBSA-PPy-MnO NPs（GOx 代表葡萄糖氧化酶，M 代表 FeO，BSA 代表牛血清白蛋白，PPy 代表聚吡咯）开发了一种将 PTT 与葡萄糖触发的化学动力学疗法（CDT）和谷胱甘肽（GSH）触发的缺氧缓解相结合的多功能治疗平台。GOx@MBSA-PPy-MnO NPs 具有优异的光热效率，并能释放 Mn，Mn 通过类芬顿反应催化 HO 转化为羟基自由基（·OH）和 O，有效破坏癌细胞并缓解肿瘤缺氧。同时，通过葡萄糖的 GOx 催化作用产生了高含量的 HO，进一步提高了 CDT 效率。此外，体内和体外实验表明，GOx@MBSA-PPy-MnO NPs 的 PTT/葡萄糖触发的 CDT 作用和缺氧缓解的联合作用可抑制癌细胞增殖并有效抑制肿瘤。总之，这项工作提供了协同治疗的证据，与对照组相比，显著提高了治疗效果并显著延长了小鼠的寿命。
