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一种基于近红外光增强药物释放和 GSH 耗竭增强类 Fenton 反应的新型多功能蛋黄壳纳米体系,用于协同癌症治疗。

A novel versatile yolk-shell nanosystem based on NIR-elevated drug release and GSH depletion-enhanced Fenton-like reaction for synergistic cancer therapy.

机构信息

School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 210089, PR China.

School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 210089, PR China.

出版信息

Colloids Surf B Biointerfaces. 2020 May;189:110810. doi: 10.1016/j.colsurfb.2020.110810. Epub 2020 Jan 20.

DOI:10.1016/j.colsurfb.2020.110810
PMID:32014651
Abstract

In this study, a versatile doxorubicin (DOX)-loaded yolk-shell nano-particles (HMCMD) assembled with manganese dioxide (MnO) as the core and copper sulfide (HMCuS) as the mesoporous (∼ 6.4 nm) shell, was designed and synthesized. The resulting HMCMD possess excellent photothermal conversion efficiency. The DOX release from the yolk-shell nanoparticles could be promoted by laser irradiation, which increased the chemotherapy of DOX. Meanwhile, Mn could be released from the HMCMD through a redox reaction between MnO and abundant glutathione (GSH) in tumor cells. The released Mn could promote the decomposition of the intracellular hydrogen peroxide (HO) by Fenton-like reaction to generate the highly toxic hydroxyl radicals (·OH), thus exhibiting the effective chemodynamic therapy (CDT). Additionally, the efficiency of Mn-mediated CDT could be effectively enhanced by NIR irradiation. Further modification of polyethylene glycol (PEG) would improve the water solubility of the HMCMD to promote the uptake by MCF-7 cells. Hence, the HMCMD with synergistic effects of chemotherapy and chemodynamic/photothermal therapy would provide an alternative strategy in antitumor research.

摘要

在这项研究中,设计并合成了一种多功能阿霉素(DOX)负载的蛋黄壳纳米粒子(HMCMD),由二氧化锰(MnO)作为核和硫化铜(HMCuS)作为介孔(∼6.4nm)壳。所得的 HMCMD 具有优异的光热转换效率。激光照射可以促进蛋黄壳纳米粒子中 DOX 的释放,从而增加 DOX 的化疗效果。同时,Mn 可以通过 MnO 与肿瘤细胞中丰富的谷胱甘肽(GSH)之间的氧化还原反应从 HMCMD 中释放出来。释放的 Mn 可以通过芬顿样反应促进细胞内过氧化氢(HO)的分解,生成高毒性的羟基自由基(·OH),从而表现出有效的化学动力学治疗(CDT)。此外,近红外(NIR)照射可以有效增强 Mn 介导的 CDT 效率。进一步修饰聚乙二醇(PEG)可以提高 HMCMD 的水溶性,促进 MCF-7 细胞的摄取。因此,具有化学动力学/光热治疗协同作用的 HMCMD 将为抗肿瘤研究提供一种替代策略。

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