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Hypoxia‐Responsive Gene Editing to Reduce Tumor Thermal Tolerance for Mild‐Photothermal Therapy
Author(s) -
Li Xueqing,
Pan Yongchun,
Chen Chao,
Gao Yanfeng,
Liu Xinli,
Yang Kaiyong,
Luan Xiaowei,
Zhou Dongtao,
Zeng Fei,
Han Xin,
Song Yujun
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202107036
Subject(s) - photothermal therapy , nanorod , genome editing , tumor microenvironment , tumor hypoxia , hypoxia (environmental) , genetic enhancement , in vivo , crispr , chemistry , cancer research , biophysics , nanotechnology , materials science , gene , biochemistry , biology , medicine , radiation therapy , organic chemistry , tumor cells , oxygen , microbiology and biotechnology
Near‐infrared (NIR)‐light‐triggered photothermal therapy (PTT) is usually associated with undesirable damage to healthy organs nearby due to the high temperatures (>50 °C) available for tumor ablation. Low‐temperature PTT would therefore have tremendous value for clinical application. Here, we construct a hypoxia‐responsive gold nanorods (AuNRs)‐based nanocomposite of CRISPR‐Cas9 for mild‐photothermal therapy via tumor‐targeted gene editing. AuNRs are modified with azobenzene‐4,4′‐dicarboxylic acid ( p ‐AZO) to achieve on‐demand release of CRISPR‐Cas9 using hypoxia‐responsive azo bonds. In the hypoxic tumor microenvironment, the azo groups of the hypoxia‐activated CRISPR‐Cas9 nanosystem based on gold nanorods (APACPs) are selectively reduced by the overexpression of reductases, leading to the release of Cas9 and subsequent gene editing. Owing to the knockout of HSP90α for reducing the thermal resistance of cancer cells, highly effective tumor ablation both in vitro and in vivo was achieved with APACPs under mild PTT.