Department of Chemistry , Jinan University , Guangzhou , 510632 , People's Republic of China.
Center for Biomedical Materials and Interfaces, Shenzhen Institutes of Advanced Technology , Chinese Academy of Sciences , Shenzhen , 518055 , People's Republic of China.
ACS Nano. 2018 Dec 26;12(12):12401-12415. doi: 10.1021/acsnano.8b06483. Epub 2018 Nov 12.
Cancer radiotherapy suffers from drawbacks such as radiation resistance of hypoxic cells, excessive radiation that causes damage of adjacent healthy tissues, and concomitant side effects. Hence, radiotherapy sensitizers with improved radiotherapeutic performance and requiring a relatively small radiation dose are highly desirable. In this study, a nanosystem based on poly(lactic- co-glycolic acid) (PLGA) and ultrasmall black phosphorus quantum dots (BPQDs) is designed and prepared to accomplish precise tumor radiosensitization. The PLGA nanoparticles act as carriers to package the BPQDs to avoid off-target release and rapid degradation during blood circulation. The nanosystem that targets the polypeptide peptide motif Arg-Gly-Asp-Gys actively accumulates in tumor tissues. The 2,3-dimethylmaleic anhydride shell decomposes in an acidic microenvironment, and the nanoparticles become positively charged, thereby favoring cellular uptake. Furthermore, glutathione (GSH) deoxidizes the disulfide bond of cystamine and sequentially triggers release of BPQDs, rendering tumor cells sensitive to radiotherapy. The treatment utilizing the PLGAD@BPQDs nanosystem and X-ray induces cell apoptosis triggered by overproduction of reactive oxygen species. In the in vivo study, the nanosystem shows excellent radiotherapy sensitization efficiency but negligible histological damage of the major organs. This study provides insights into the design and fabrication of surface-charge-switching and pH-responsive nanosystems as potent radiosensitizers to achieve excellent radiotherapy sensitization efficacy and negligible toxic side effects.
癌症放射疗法存在一些缺点，如缺氧细胞的辐射抗性、过度辐射导致相邻健康组织损伤以及伴随的副作用。因此，人们非常希望开发具有改善放射治疗性能且需要相对较小辐射剂量的放射增敏剂。在本研究中，设计并制备了一种基于聚（乳酸-共-乙醇酸）（PLGA）和超小黑磷量子点（BPQDs）的纳米系统，以实现精确的肿瘤放射增敏。PLGA 纳米粒作为载体来包封 BPQDs，以避免在血液循环过程中发生非靶向释放和快速降解。靶向多肽肽基序 Arg-Gly-Asp-Gys 的纳米系统主动积聚在肿瘤组织中。2,3-二甲基马来酸酐壳在酸性微环境中分解，纳米粒带正电荷，从而有利于细胞摄取。此外，谷胱甘肽（GSH）将胱胺的二硫键还原，并依次触发 BPQDs 的释放，使肿瘤细胞对放射治疗敏感。利用 PLGAD@BPQDs 纳米系统和 X 射线进行治疗会导致活性氧过度产生引发细胞凋亡。在体内研究中，该纳米系统表现出优异的放射增敏效率，但对主要器官的组织损伤可忽略不计。本研究为设计和制造表面电荷转换和 pH 响应纳米系统作为有效的放射增敏剂提供了思路，以实现优异的放射增敏效果和可忽略的毒副作用。
