药物输送
神经保护
细胞凋亡
间充质干细胞
血管生成
炎症
全身给药
基质金属蛋白酶
医学
药理学
癌症研究
化学
免疫学
纳米技术
材料科学
生物
病理
体内
内科学
生物化学
生物技术
作者
Yang You,Jianpei Xu,Yipu Liu,Haichun Li,Laozhi Xie,Chuchu Ma,Yinzhe Sun,Shiqiang Tong,Kaifan Liang,Songlei Zhou,Fenfen Ma,Qingxiang Song,Wenze Xiao,Kaikai Fu,Chengxiang Dai,Suke Li,Jigang Lei,Qiyong Mei,Xiaoling Gao,Jun Chen
出处
期刊:ACS Nano
[American Chemical Society]
日期:2023-04-26
卷期号:17 (9): 8646-8662
被引量:31
标识
DOI:10.1021/acsnano.3c01497
摘要
Apoptotic vesicles (ApoVs) hold great promise for inflammatory regulation and tissue repair. However, little effort has been dedicated to developing ApoV-based drug delivery platforms, while the insufficient targeting capability of ApoVs also limits their clinical applications. This work presents a platform architecture that integrates apoptosis induction, drug loading, and functionalized proteome regulation, followed by targeting modification, enabling the creation of an apoptotic vesicle delivery system to treat ischemic stroke. Briefly, α-mangostin (α-M) was utilized to induce mesenchymal stem cell (MSC) apoptosis while being loaded onto MSC-derived ApoVs as an anti-oxidant and anti-inflammatory agent for cerebral ischemia/reperfusion injury. Matrix metalloproteinase activatable cell-penetrating peptide (MAP), a microenvironment-responsive targeting peptide, was modified on the surface of ApoVs to obtain the MAP-functionalized α-M-loaded ApoVs. Such engineered ApoVs targeted the injured ischemic brain after systemic injection and achieved an enhanced neuroprotective activity due to the synergistic effect of ApoVs and α-M. The internal protein payloads of ApoVs, upon α-M activation, were found engaged in regulating immunological response, angiogenesis, and cell proliferation, all of which contributed to the therapeutic effects of ApoVs. The findings provide a universal framework for creating ApoV-based therapeutic drug delivery systems for the amelioration of inflammatory diseases and demonstrate the potential of MSC-derived ApoVs to treat neural injury.
科研通智能强力驱动
Strongly Powered by AbleSci AI