Ma Haijun, Zhang Xiaoyan, Yang Yang, Li Shumu, Huo Jiawei, Liu Yang, Guan Mirong, Zhen Mingming, Shu Chunying, Li Jie, Wang Chunru
Beijing National Research Center for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Science, Beijing 100190, China.
Department of General Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.
Langmuir. 2021 Mar 2;37(8):2740-2748. doi: 10.1021/acs.langmuir.0c03483. Epub 2021 Feb 14.
Hydrophilic fullerene derivatives get notable performance in various biological applications, especially in cancer therapy and antioxidation. The biological behaviors of functional fullerenes are much dependent on their surface physicochemical properties. The excellent reactive oxygen species-scavenging capabilities of functional fullerenes promote their outstanding performances in inhibiting pathological symptoms associated with oxidative stress, including neurodegenerative diseases, cardiovascular diseases, acute and chronic kidney disease, and diabetes. Herein, fullerene derivatives with reversed surface charges in aqueous solutions are prepared: cationic C-EDA and anionic C-(EDA-EA). Under the driving force of membrane potential (negative inside) in the cell and mitochondria, C-EDA is much rapidly taken in by cells and transported into mitochondria compared with C-(EDA-EA) that is enriched in lysosomes. With high cellular uptake and mitochondrial enrichment, C-EDA exhibits stronger antioxidation capabilities than C-(EDA-EA), indicating its better performance in the therapy of oxidation-induced diseases. It is revealed that the cellular uptake rate, subcellular location, and intracellular antioxidation behavior of fullerene derivatives are primarily mediated by their surface charges, providing new strategies for the design of fullerene drugs and their biological applications.
亲水性富勒烯衍生物在各种生物应用中表现出色，尤其是在癌症治疗和抗氧化方面。功能性富勒烯的生物学行为很大程度上取决于其表面物理化学性质。功能性富勒烯出色的活性氧清除能力促进了它们在抑制与氧化应激相关的病理症状方面的卓越表现，这些病理症状包括神经退行性疾病、心血管疾病、急性和慢性肾病以及糖尿病。在此，制备了在水溶液中具有相反表面电荷的富勒烯衍生物：阳离子型C-EDA和阴离子型C-(EDA-EA)。在细胞和线粒体膜电位（内部为负）的驱动下，与富集在溶酶体中的C-(EDA-EA)相比，C-EDA被细胞摄取并转运到线粒体中的速度要快得多。由于具有高细胞摄取率和线粒体富集，C-EDA表现出比C-(EDA-EA)更强的抗氧化能力，表明其在氧化诱导疾病治疗中具有更好的性能。研究表明，富勒烯衍生物的细胞摄取率、亚细胞定位和细胞内抗氧化行为主要由其表面电荷介导，为富勒烯药物的设计及其生物应用提供了新策略。
