喜树碱
前药
细胞凋亡
细胞毒性
癌症研究
细胞内
缺氧(环境)
细胞生物学
肿瘤细胞
化学
渗透(战争)
体外
药理学
生物
生物化学
工程类
有机化学
氧气
运筹学
作者
Dongyang Zhao,Wenhui Tao,Songhao Li,Yao Chen,Yinghua Sun,He Zhang,Bingjun Sun,Jin Sun
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2021-04-16
卷期号:7 (16)
被引量:59
标识
DOI:10.1126/sciadv.abg0880
摘要
Chemotherapeutic nanomedicines can exploit the neighboring effect to increase tumor penetration. However, the neighboring effect is limited, likely by the consumption of chemotherapeutic agents and resistance of internal hypoxic tumor cells. Here, we first propose and demonstrate that apoptotic bodies (ApoBDs) could carry the remaining drugs to neighboring tumor cells after apoptosis. To enhance the ApoBD-based neighboring effect, we fabricated disulfide-linked prodrug nanoparticles consisting of camptothecin (CPT) and hypoxia-activated prodrug PR104A. CPT kills external normoxic tumor cells to produce ApoBDs, while PR104A remains inactive. The remaining drugs could be effectively delivered into internal tumor cells via ApoBDs. Although CPT exhibits low toxicity to internal hypoxic tumor cells, PR104A could be activated to exert strong cytotoxicity, which further facilitates deep penetration of the remaining drugs. Such a synergic approach could overcome the limitations of the neighboring effect to penetrate deep into solid tumors for whole tumor destruction.
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