An exosome-like programmable-bioactivating paclitaxel prodrug nanoplatform for enhanced breast cancer metastasis inhibition.

Autor: Wang K; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Ye H; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Zhang X; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Wang X; School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Yang B; State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China., Luo C; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Zhao Z; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Zhao J; School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Lu Q; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Zhang H; School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Kan Q; School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Wang Y; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., He Z; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China., Sun J; Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China. Electronic address: sunjin@syphu.edu.cn.
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2020 Oct; Vol. 257, pp. 120224. Date of Electronic Publication: 2020 Jul 15.
DOI: 10.1016/j.biomaterials.2020.120224
Abstrakt: Metastasis is closely associated with high breast cancer mortality. Although nanotechnology-based anti-metastatic treatments have developed rapidly, the anti-metastasis efficiency is still far from satisfactory, mainly due to the poor recognition of circulating tumor cells (CTCs) in blood. Herein, we developed an exosome-like sequential-bioactivating prodrug nanoplatform (EMPCs) to overcome the obstacle. Specifically, the reactive oxygen species (ROS)-responsive thioether-linked paclitaxel-linoleic acid conjugates (PTX-S-LA) and cucurbitacin B (CuB) are co-encapsulated into polymeric micelles, and the nanoparticles are further decorated with exosome membrane (EM). The resulting EMPCs could specifically capture and neutralize CTCs during blood circulation through the high-affinity interaction between cancer cell membrane and homotypic EM. Following cellular uptake, EMPCs first release CuB, remarkably blocking tumor metastasis via downregulation of the FAK/MMP signaling pathway. Moreover, CuB obviously elevates the intracellular oxidative level to induce a sequential bioactivation of ROS-responsive PTX-S-LA. In vitro and in vivo results demonstrate that EMPCs not only exhibit amplified prodrug bioactivation, prolonged blood circulation, selective targeting of homotypic tumor cells, and enhanced tumor penetration, but also suppress tumor metastasis through CTCs clearance and FAK/MMP signaling pathway regulation. This study proposes an integrated approach for mechanism-based inhibition of tumor metastasis and manifests a promising potential of programmable-bioactivating prodrug nanoplatform for cancer metastasis inhibition.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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