2. Academic Validation
  3. Low-temperature photothermal irradiation triggers alkyl radicals burst for potentiating cancer immunotherapy

Low-temperature photothermal irradiation triggers alkyl radicals burst for potentiating cancer immunotherapy

  • J Colloid Interface Sci. 2022 May 15;614:436-450. doi: 10.1016/j.jcis.2022.01.131.
Bo Ning 1,  Yao Liu 2,  Boshu Ouyang 3,  Xiaomin Su 1,  Huishu Guo 4,  Zhiqing Pang 5,  Shun Shen 6
Affiliations

Affiliations

  • 1 Central Laboratory, First Affiliated Hospital, Dalian Medical University, Dalian 116021, China; Pharmacy Department & Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China; The Institute of Integrative Medicine, Dalian Medical University, Dalian 116021, China.
  • 2 The Institute for Translational Nanomedicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
  • 3 Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China; Institutes of Integrative Medicine, Fudan University, Shanghai, China.
  • 4 Central Laboratory, First Affiliated Hospital, Dalian Medical University, Dalian 116021, China; The Institute of Integrative Medicine, Dalian Medical University, Dalian 116021, China. Electronic address: [email protected].
  • 5 School of Pharmacy & Key Laboratory of Smart Drug Delivery, Fudan University, Shanghai 201203, China. Electronic address: [email protected].
  • 6 Pharmacy Department & Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China. Electronic address: [email protected].
PMID: 35108635 DOI: 10.1016/j.jcis.2022.01.131
Abstract

Although low-temperature photothermal therapy (PTT) can sensitize tumors to immune checkpoint inhibition, its efficacy is still restricted in the deep and internal tumors without enough oxygen and lymphocytic infiltration. Non-oxygen-dependent alkyl radicals have been demonstrated to synergistically enhance PTT through up-regulating lipid peroxidation and Reactive Oxygen Species (ROS). Herein, an innovative strategy based on alkyl radicals to augment immunogenetic cell death (ICD) caused by mild PTT was proposed to improve poor efficacy of immunotherapy, which composed of a photothermal material of Chinse ink, an azo-initiator of 2,2-azobis[2-(2-imidazoline-2-acyl)propane]dihydrochloride (AIPH) and a PD-L1 inhibitor of HY19991 (HY). Upon near-infrared-II laser irradiation, low-temperature (<45℃) stimulation induced a high expression of immune checkpoint receptor (PD-L1) in tumors and triggered a large amount alkyl radicals generated by AIPH. Significantly, the alkyl radicals augmented the ICD and increased the recruitment of tumor-infiltrating lymphocytes against tumors after transformation of the immunologically cold tumor microenvironment into hot by mild PTT. The released HY further enhanced the immunotherapy effect by blocking the binding of activated T lymphocytes and PD-L1. In vivo studies exhibited that the all-in-one hydrogel with synergistic mechanisms had an extraordinary ability to reverse the immunosuppressive microenvironment, stimulate innate and adaptive immune responses to eliminate tumors and prevent metastasis.

Keywords

Alkyl radical; Immune checkpoint blocking therapy; Immunogenic cell death; Low-temperature photothermal therapy.

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