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双谷胱甘肽耗竭增强半金属VSe/Mn-CS上热疗辅助肿瘤治疗的酶催化活性

Dual Glutathione Depletion Enhanced Enzyme Catalytic Activity for Hyperthermia Assisted Tumor Therapy on Semi-Metallic VSe/Mn-CS.

作者信息

Zhao Ruoxi, Zhu Yanlin, Zhou Jialing, Liu Bin, Du Yaqian, Gai Shili, Shen Ruifang, Feng Lili, Yang Piaoping

机构信息

Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin, 150001, P. R. China.

Yantai Research Institute, Harbin Engineering University, Yantai, 264000, P. R. China.

出版信息

ACS Nano. 2022 Jul 26;16(7):10904-10917. doi: 10.1021/acsnano.2c03222. Epub 2022 Jul 7.

Abstract

Semimetallic nanomaterials as photothermal agents for bioimaging and cancer therapy have attracted tremendous interest. However, the poor photothermal stability, low biocompatibility, and single component limit their therapeutic efficiency in cancer treatment. Here, manganese-doped VSe semimetallic nanosheets were prepared and subsequently modified with chitosan (named VSe/Mn-CS NSs) for combined enzyme catalytic and photothermal therapy. VSe/Mn-CS NSs show high photothermal property with a photothermal conversion efficiency of 34.61% upon 808 nm near-infrared laser irradiation. In the tumor microenvironment, VSe/Mn-CS NSs can convert endogenous HO into lethal hydroxyl radicals (•OH) to induce cancer cell apoptosis. The interaction between glutathione (GSH) and Se-Se bonds in VSe/Mn-CS NSs results in the depletion of GSH level, and the valence states transition of manganese ions is also beneficial for the GSH consumption. This dual depletion of GSH markedly enhances the peroxidase (POD) activity, leading to the high •OH production and the improved therapeutic effect. What is more, the -weighted magnetic resonance and photoacoustic imaging endow VSe/Mn-CS NSs with the ability to guide and track the treatment process. Our study provides a research strategy for the application of semimetallic nanomaterials in cancer diagnosis and treatment.

摘要

半金属纳米材料作为用于生物成像和癌症治疗的光热剂已引起了极大的关注。然而,其较差的光热稳定性、低生物相容性以及单一成分限制了它们在癌症治疗中的治疗效果。在此,制备了锰掺杂的VSe半金属纳米片,随后用壳聚糖进行修饰(命名为VSe/Mn-CS NSs)以用于联合酶催化和光热治疗。在808 nm近红外激光照射下,VSe/Mn-CS NSs表现出高光热性能,光热转换效率为34.61%。在肿瘤微环境中,VSe/Mn-CS NSs可将内源性H₂O₂转化为致命的羟基自由基(•OH)以诱导癌细胞凋亡。VSe/Mn-CS NSs中谷胱甘肽(GSH)与Se-Se键之间的相互作用导致GSH水平的消耗,并且锰离子的价态转变也有利于GSH的消耗。这种GSH的双重消耗显著增强了过氧化物酶(POD)活性,导致产生高浓度的•OH并改善了治疗效果。此外,加权磁共振和光声成像赋予VSe/Mn-CS NSs引导和跟踪治疗过程的能力。我们的研究为半金属纳米材料在癌症诊断和治疗中的应用提供了一种研究策略。

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