替莫唑胺
微泡
药物输送
外体
免疫原性
胶质瘤
化学
癌症研究
适体
药品
靶向给药
血脑屏障
纳米载体
药理学
医学
生物
免疫系统
免疫学
中枢神经系统
小RNA
分子生物学
内科学
生物化学
有机化学
基因
作者
Shifu Liang,Hao Xu,Bang‐Ce Ye
出处
期刊:Langmuir
[American Chemical Society]
日期:2021-12-22
卷期号:38 (1): 299-308
被引量:21
标识
DOI:10.1021/acs.langmuir.1c02500
摘要
Glioblastoma multiforme (GBM) is the most aggressive tumor of the central nervous system in adults. The standard therapy of GBM fails to eradicate it due to the drug resistance of glioblastoma stem cells (GSCs) and the presence of the blood-brain-barrier (BBB). Temozolomide (TMZ) is the first-line anti-GBM drug after surgery. However, the high activity of O6-alkylguanine-DNA alkyltransferase (AGT) limits the therapeutic effect of TMZ. Herein, we reported dual-receptor-specific exosomes as vehicles loaded with TMZ and O6-benzylguanine (BG) for eradicating TMZ-resistant GBM. Exosomes pose great promise as nanocarriers due to their intrinsic low immunogenicity, strong cargo-protective capacity, ideal size range, and natural penetration ability of the blood-brain-barrier (BBB). The target ligands angiopep-2 and CD133 RNA aptamers were conjugated on exosomes via an amphiphilic molecule bridge, which was induced to express on donor cells. The resulting nanocarriers exhibited efficient uptake by U87MG and GSCs, excellent BBB penetration ability, and perfect GBM accumulation due to An2 and CD133 aptamer functionalization. Such superior properties of the two dual-receptor-specific exosomes resulted in excellent in vitro proliferation inhibition of U87MG and GSCs and extension of the median survival time of U87MG-bearing mice, without causing adverse effects. The formed exosome nanocomposites can serve as powerful nanomedicine for GBM therapy and provide a promising avenue for targeted therapy against other diseases of the central nervous system.
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