Near-infrared(NIR)-light-triggered nanomedicine,including photodynamic therapy(PDT)and photothermal therapy(PTT),is growing an attractive approach for cancer therapy due to its high spatiotemporal controllability and minimal invasion,but the tumor eradication is limited by the intrinsic anti-stress response of tumor cells.Herein,we fabricate a tumor-microenvironment responsive CRISPR nanoplatform based on oxygen-deficient titania(TiO2-x)for mild NIR-phototherapy.In tumor microenvi-ronment,the overexpressed hyaluronidase(HAase)and glutathione(GSH)can readily destroy hyaluronic acid(HA)and disulfide bond and releases the Cas9/sgRNA from TiO2-x to target the stress alleviating regulators,i.e.,nuclear factor E2-related factor 2(NRF2)and heat shock protein 90α(HSP90α),thereby reducing the stress tolerance of tumor cells.Under subsequent NIR light illumination,the TiO2-x demon-strates a higher anticancer effect both in vitro and in vivo.This strategy not only provides a promising modality to kills cancer cells in a minimal side-effects manner by interrupting anti-stress pathways but also proposes a general approach to achieve controllable gene editing in tumor region without unwanted genetic mutation in normal environments.

Zekun Li;Yongchun Pan;Shiyu Du;Yayao Li;Chao Chen;Hongxiu Song;Yueyao Wu;Xiaowei Luan;Qin Xu;Xiaoxiang Guan;Yujun Song;Xin Han

Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica,School of Medicine&Holistic Integrative Medicine,Jiangsu Joint International Research Laboratory of Chinese Medicine and Regenerative Medicine,Nanjing University of Chinese Medicine,Nanjing 210023,China;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;Department of Oncology,The First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China

药学学报（英文版）

[1]Zekun Li;Yongchun Pan;Shiyu Du;Yayao Li;Chao Chen;Hongxiu Song;Yueyao Wu;Xiaowei Luan;Qin Xu;Xiaoxiang Guan;Yujun Song;Xin Han-.Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy)[J].药学学报（英文版）,2022(11):4224-4234

nanoprodrug,microenvi

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