Zhuang Hongjun, He Xiaofang, Li Huiyan, Chen Yang, Wu Tong, Jiang Xingwu, Zhang Huilin, Zhao Peiran, Wang Ya, Chen Jian, Zhang Jian, Liu Yanyan, Bu Wenbo
Departments of Rehabilitation, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China.
Department of Materials Science and State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200433, P.R. China.
ACS Nano. 2023 Jul 25;17(14):13872-13884. doi: 10.1021/acsnano.3c03670. Epub 2023 Jul 17.
"Structure subserves function" is one fundamental biological maxim, and so the biological membrane that delimits the regions primarily serves as the margin between life and death for individual cells. Here, an Oswald ripening mechanism-guided solvothermal method was proposed for the synthesis of uniform MnS nanocapsules assembled with metastable γ-MnS nanocrystals. Through designing the physicochemical properties, MnS nanocapsules would disaggregate into small γ-MnS nanocrystals in a tumor acidic environment, with the surface potential switched from negative to positive, thus showing conspicuous delivery performance. More significantly, the specific accumulation of Mn in mitochondria was promoted due to the downregulation of mitochondrial calcium uptake 1 (MICU1) by the formed HS, thus leading to serious mitochondrial Mn-poisoning for membrane permeability increase and then tumor apoptosis. This study provides a synthesis strategy of metal sulfide nanocapsules and encourages multidisciplinary researchers to focus on ion-cancer crosstalk for the development of an antitumor strategy.
“结构决定功能”是一条基本的生物学准则，因此界定区域的生物膜主要充当单个细胞生与死的界限。在此，提出了一种奥斯特瓦尔德熟化机制引导的溶剂热法来合成由亚稳态γ-MnS纳米晶体组装而成的均匀MnS纳米胶囊。通过设计物理化学性质，MnS纳米胶囊在肿瘤酸性环境中会分解成小的γ-MnS纳米晶体，表面电位从负变为正，从而表现出显著的递送性能。更重要的是，所形成的HS下调线粒体钙摄取1（MICU1），促进了Mn在线粒体中的特异性积累，从而导致严重的线粒体Mn中毒，使膜通透性增加，进而导致肿瘤细胞凋亡。本研究提供了一种金属硫化物纳米胶囊的合成策略，并鼓励多学科研究人员关注离子与癌症的相互作用，以开发抗肿瘤策略。
