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

• Published in: Advanced functional materials Vol. 31; no. 24
• Main Authors: Liu, Xin, Yang, Yuanyuan, Ling, Mingjian, Sun, Rui, Zhu, Meiyan, Chen, Jianjun, Yu, Meng, Peng, Zhenwei, Yu, Zhiqiang, Liu, Xiqiang
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc 01.06.2021
• Subjects: azo‐containing polymers; Breast cancer; Carbon; Cell cycle; Cell death; Deoxyribonucleic acid; DNA; Endoplasmic reticulum; Gene sequencing; Hypoxia; hypoxic tumors; Materials science; Near infrared radiation; NIR II photothermal therapy; Polymers; Robustness; Therapy; thermodynamic therapy; Toxicity; Tumors; Xenotransplantation
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.202101709

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. A near‐infrared II (NIR II) laser activatable nanomedicine (P2@IR1061‐arginine‐glycine‐aspartic acid (RGD)) is developed to realize safe and efficient combined photothermal and thermodynamic therapy (PTT/TDT) on both a 4T1 tumor model and a patient‐derived tumor xenograft model of hepatocellular carcinoma (patient‐derived xenograft (PDX)HCC). P2@IR1061‐RGD with NIR II laser irradiation overcomes hypoxia‐relative therapeutic resistance via photothermal effects and robust carbon radical generation.