Spatiotemporally Targeted Nanomedicine Overcomes Hypoxia-Induced Drug Resistance of Tumor Cells after Disrupting Neovasculature.

Nano Letters
Jinjin ChenXuesi Chen

Abstract

Vascular disrupting agents (VDAs) are emerging anticancer agents, which show rising demand for combination with cytostatic drugs (CSDs), owing to inadequate tumor inhibition when applied singly. Nevertheless, the combination remains a challenge due to the different working sites of VDAs and CSDs and hypoxia-induced drug resistance after disrupting neovasculature by VDAs. Herein, we developed a shell-stacked nanoparticle (SNP) for coencapsulation of a VDA combretastatin A-4 phosphate (CA4P) and a proteasome inhibitor bortezomib (BTZ). The SNP could spatiotemporally deliver CA4P to tumor neovasculature and BTZ to tumor cells mediated by the site-specific stimuli-activated drug release. Moreover, the SNP also reversed the drug resistance caused by the overexpressed ABCG2 under CA4P-induced hypoxic conditions. The spatiotemporally targeted combination therapy significantly inhibited the growth of both the human A549 pulmonary adenocarcinoma xenograft model and patient-derived xenograft (PDX) model of colon cancer in mice, providing a promising strategy for treating advanced cancers.

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Citations

Jan 6, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Yan ChenWei Huang
Jan 23, 2021·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Duoyi ZhaoXuesi Chen
Feb 6, 2021·Nanomedicine·Lingyu WeiJianxun Ding
Dec 18, 2020·Frontiers in Bioengineering and Biotechnology·Jie LiChangfeng Fu
Jan 8, 2021·Frontiers in Bioengineering and Biotechnology·Jingying XuJidong Wang
Jan 12, 2021·Frontiers in Bioengineering and Biotechnology·Qian SunJing Ma
Feb 23, 2021·Macromolecular Bioscience·Yunqi GuoXiangyang Shi
Apr 14, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yuheng WangZhishen Ge
May 18, 2021·Frontiers in Oncology·Yan-Qi LiJi-Gang Dai
Jul 8, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Guorong ZhangWei Han
Nov 3, 2021·Nano Convergence·Jessica A Kemp, Young Jik Kwon

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