Hypoxia-Responsive Gene Editing to Reduce Tumor Thermal Tolerance for Mild-Photothermal Therapy
Xueqing Li
College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, 210023 China
These authors contributed equally to this work.
Search for more papers by this authorYongchun Pan
College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, 210023 China
These authors contributed equally to this work.
Search for more papers by this authorChao Chen
School of Medicine & Holistic Integrative Medicine, Jiangsu Collaborative Innovation Canter of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, 210023 China
Search for more papers by this authorDr. Yanfeng Gao
College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, 210023 China
Search for more papers by this authorDr. Xinli Liu
College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, 210023 China
Search for more papers by this authorDr. Kaiyong Yang
School of Medicine & Holistic Integrative Medicine, Jiangsu Collaborative Innovation Canter of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, 210023 China
Search for more papers by this authorXiaowei Luan
College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, 210023 China
Search for more papers by this authorDongtao Zhou
College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, 210023 China
Search for more papers by this authorFei Zeng
College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, 210023 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Xin Han
School of Medicine & Holistic Integrative Medicine, Jiangsu Collaborative Innovation Canter of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, 210023 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Yujun Song
College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, 210023 China
Search for more papers by this authorXueqing Li
College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, 210023 China
These authors contributed equally to this work.
Search for more papers by this authorYongchun Pan
College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, 210023 China
These authors contributed equally to this work.
Search for more papers by this authorChao Chen
School of Medicine & Holistic Integrative Medicine, Jiangsu Collaborative Innovation Canter of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, 210023 China
Search for more papers by this authorDr. Yanfeng Gao
College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, 210023 China
Search for more papers by this authorDr. Xinli Liu
College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, 210023 China
Search for more papers by this authorDr. Kaiyong Yang
School of Medicine & Holistic Integrative Medicine, Jiangsu Collaborative Innovation Canter of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, 210023 China
Search for more papers by this authorXiaowei Luan
College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, 210023 China
Search for more papers by this authorDongtao Zhou
College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, 210023 China
Search for more papers by this authorFei Zeng
College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, 210023 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Xin Han
School of Medicine & Holistic Integrative Medicine, Jiangsu Collaborative Innovation Canter of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, 210023 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Yujun Song
College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, 210023 China
Search for more papers by this authorAbstract
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.
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