Li Xiang, He Mei, Zhou Qinghao, Dutta Debabrata, Lu Nannan, Li Shikuo, Ge Zhishen
CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, 230026Anhui, China.
School of Materials Science and Engineering, Anhui University, Hefei230601, P.R. China.
ACS Appl Mater Interfaces. 2022 Nov 16;14(45):50601-50615. doi: 10.1021/acsami.2c15406. Epub 2022 Nov 6.
The unique tumor microenvironment (TME) characteristic of severe hypoxia, overexpressed intracellular glutathione (GSH), and elevated hydrogen peroxide (HO) concentration limit the anticancer effect by monotherapy. In this report, glucose oxidase (GOx)-encapsulated mesoporous hollow CoS nanoreactors are constructed with the coverage of polyphenol diblock polymers containing poly(oligo(ethylene glycol) methacrylate) and dopamine moieties containing methacrylate polymeric block, which are termed as GOx@PCoS. After intravenous injection, tumor accumulation, and cellular uptake, GOx@PCoS deplete GSH by Co ions. GOx inside the nanoreactors produce HO via oxidation of glucose to enhance •OH-based chemodynamic therapy (CDT) through the Fenton-like reaction under the catalysis of Co. Moreover, Co ions possess catalase activity to catalyze production of O from HO to relieve tumor hypoxia. Upon 808 nm laser irradiation, GOx@PCoS exhibit photothermal and photodynamic effects with a high photothermal conversion efficiency (45.06%) and generation capacity of the toxic superoxide anion (•O) for photothermal therapy (PTT) and photodynamic therapy (PDT). The synergetic antitumor effects can be realized by GSH depletion, starvation, and combined CDT, PTT, and PDT with enhanced efficacy. Notably, GOx@PCoS can also be used as a magnetic resonance imaging (MRI) contrast agent to monitor the antitumor performance. Thus, GOx@PCoS show great potentials to effectively modulate TME and perform synergistic multimodal therapy.
严重缺氧、细胞内谷胱甘肽（GSH）过表达以及过氧化氢（HO）浓度升高所特有的肿瘤微环境（TME）限制了单一疗法的抗癌效果。在本报告中，构建了包封葡萄糖氧化酶（GOx）的介孔中空CoS纳米反应器，其表面覆盖有包含聚（甲基丙烯酸寡聚乙二醇酯）的多酚二嵌段聚合物和含有甲基丙烯酸酯聚合物嵌段的多巴胺部分，被称为GOx@PCoS。静脉注射后，通过肿瘤蓄积和细胞摄取，GOx@PCoS通过Co离子消耗GSH。纳米反应器内的GOx通过葡萄糖氧化产生HO，以在Co的催化下通过类芬顿反应增强基于•OH的化学动力学疗法（CDT）。此外，Co离子具有过氧化氢酶活性，可催化HO产生O以缓解肿瘤缺氧。在808 nm激光照射下，GOx@PCoS表现出光热和光动力效应，具有高光热转换效率（45.06%）以及用于光热疗法（PTT）和光动力疗法（PDT）的有毒超氧阴离子（•O）生成能力。通过GSH消耗、饥饿以及联合CDT、PTT和PDT可实现协同抗肿瘤作用，疗效增强。值得注意的是，GOx@PCoS还可作为磁共振成像（MRI）造影剂来监测抗肿瘤性能。因此，GOx@PCoS在有效调节TME和实施协同多模态治疗方面显示出巨大潜力。
