Near-Infrared II Light-Triggered Robust Carbon Radical Generation for Combined Photothermal and Thermodynamic Therapy of Hypoxic Tumors

作者：Liu, Xin; Yang, Yuanyuan; Ling, Mingjian; Sun, Rui; Zhu, Meiyan; Chen, Jianjun; Yu, Meng; Peng, Zhenwei^*; Yu, Zhiqiang^*; Liu, Xiqiang^*

来源：Advanced Functional Materials, 2021, 31(24): 2101709.

DOI：10.1002/adfm.202101709

• azo&#8208
• containing polymers
• hypoxic tumors
• NIR II photothermal therapy
• thermodynamic therapy

Tumor hypoxia is a major cause of failure in cancer therapy, and there is almost no efficacious treatment for hypoxic tumors. Herein, an azo-containing polymer (P2) is designed to encapsulate IR1061, and further covalently grafted with a tumor-targeting tripeptide RGD to form P2@IR1061-RGD NPs for combined photothermal and thermodynamic therapy (PTT/TDT) in the near-infrared II (NIR II) biowindow (1000-1700 nm). Upon 1064 nm laser irradiation, IR1061 generates heat to break the azo bonds of P2, achieving robust carbon radical generation, which induces cancer cell death even under a hypoxic tumor microenvironment. RNA-sequencing is first adopted to unveil the impact of combined PTT/TDT on the cell transcriptome and the corresponding pathways using 4T1 breast cancer cells. The dysregulated genes are involved in protein processing within the endoplasmic reticulum, cell cycle regulation, ubiquitin-mediated proteolysis, and DNA replication pathways. The tumor inhibition rates on a 4T1 breast cancer model as well as on a patient-derived xenograft model of hepatocellular carcinoma (PDXHCC) are 97% and 100%, and negligible systematic toxicity is observed. This study proposes the application of an azo-containing polymer for safe and efficient combined PTT/TDT in the NIR II biowindow, as a promising strategy for clinical treatment of hypoxic tumors.

• 单位
  1; 南方医科大学; 中山大学