Tumor Microenvironment-Mediated Construction and Deconstruction of Extracellular Drug-Delivery Depots

Nano Letters
Quanyin HuZhen Gu

Abstract

Protein therapy has been considered the most direct and safe approach to treat cancer. Targeting delivery of extracellularly active protein without internalization barriers, such as membrane permeation and endosome escape, is efficient and holds vast promise for anticancer treatment. Herein, we describe a "transformable" core-shell based nanocarrier (designated CS-NG), which can enzymatically assemble into microsized extracellular depots at the tumor site with assistance of hyaluronidase (HAase), an overexpressed enzyme at the tumor microenvironment. Equipped with an acid-degradable modality, the resulting CS-NG can substantially release combinational anticancer drugs-tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) and antiangiogenic cilengitide toward the membrane of cancer cells and endothelial cells at the acidic tumor microenvironment, respectively. Enhanced cytotoxicity on MDA-MB-231 cells and improved antitumor efficacy were observed using CS-NG, which was attributed to the inhibition of cellular internalization and prolonged retention time in vivo.

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Citations

Sep 1, 2016·ACS Applied Materials & Interfaces·Quanyin HuJun Chen
Feb 1, 2017·Acta Biomaterialia·Guang-Zhi YangGareth R Williams
Mar 13, 2018·Advanced Healthcare Materials·Yesi ShiGang Liu
Jun 28, 2018·Nanoscale·Yongliang YangLixin Dong
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May 17, 2019·Advanced Healthcare Materials·Mengyao ZhaoFan Zhang
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Aug 28, 2020·Frontiers in Chemistry·Mengqian LiQi Shuai
Oct 20, 2020·Advanced Healthcare Materials·Hyeongmok ParkWon Jong Kim
Oct 27, 2020·Advanced Materials·Xiaodong ZhangYanli Zhao
Dec 5, 2020·Advanced Healthcare Materials·Yongchao YaoShiyong Zhang
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Nov 20, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Junha LimWon Jong Kim
Mar 11, 2021·Biomaterials·Yuequan WangJin Sun
Apr 20, 2021·Advanced Healthcare Materials·Qian-Ni YeJun Wang
Apr 27, 2021·ACS Nano·Qiuhong ZhangYanli Zhao

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