Apoptotic body-mediated intercellular delivery for enhanced drug penetration and whole tumor destruction.

Autor:	Zhao D; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China., Tao W; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China., Li S; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China., Chen Y; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China., Sun Y; Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China., He Z; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China., Sun B; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China., Sun J; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China. sunjin@syphu.edu.cn.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2021 Apr 16; Vol. 7 (16). Date of Electronic Publication: 2021 Apr 16 (Print Publication: 2021).
DOI:	10.1126/sciadv.abg0880
Abstrakt:	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. (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
Databáze:	MEDLINE
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