NIR-II light evokes DNA cross-linking for chemotherapy and immunogenic cell death

被引:24
作者
Huang, Yun [1 ,2 ]
Wei, Dengshuai [3 ]
Wang, Bin [3 ]
Tang, Dongsheng [3 ]
Cheng, Ailan [2 ]
Xiao, Shengjun [1 ]
Yu, Yingjie [4 ]
Huang, Weiguo [1 ,2 ]
机构
[1] Guilin Med Univ, Guangxi Key Lab Tumor Immun & Microenvironm Regula, Guilin 541199, Peoples R China
[2] Univ South China, Canc Res Inst, Hengyang Med Coll, Hengyang 421001, Peoples R China
[3] Chinese Acad Sci, Inst Chem, Beijing Natl Lab Mol Sci, State Key Lab Polymer Phys & Chem, Beijing 100190, Peoples R China
[4] Beijing Univ Chem Technol, State Key Lab Organ Inorgan Composites, Beijing Lab Biomed Mat, Beijing 100029, Peoples R China
关键词
Oxaliplatin; Mild hyperthermia; DNA damage; Immunogenic cell death; Immunotherapy; CALRETICULIN EXPOSURE; DENDRITIC CELLS; CANCER; DELIVERY; DRUGS; OXALIPLATIN; CONJUGATE; IMMUNITY;
D O I
10.1016/j.actbio.2023.02.012
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
As a DNA damaging agent, oxaliplatin (OXA) can induce immunogenic cell death (ICD) in tumors to ac-tivate the immune system. However, the DNA damage induced by OXA is limited and the ICD effect is not strong enough to enhance anti-tumor efficacy. Here, we propose a strategy to maximize the ICD ef-fect of OXA through the mild hyperthermia generated by nanoparticles with a platinum (IV) prodrug of OXA (Pt(IV)-C16) and a near-infrared-II (NIR-II) photothermal agent IR1061 upon the irradiation of NIR-II light. The mild hyperthermia (43 degrees C) holds advantages in two aspects: 1) increase the Pt-DNA cross-linking, leading to enhanced DNA damage and apoptosis; 2) induce stronger ICD effects for can-cer immunotherapy. We demonstrated that, compared with OXA and photothermal therapy of IR1061 alone, these nanoparticles under NIR-II light irradiation can significantly improve the anti-cancer efficacy against triple-negative breast cancer 4T1 tumor. This new strategy provides an effective way to improve the therapeutic outcome of OXA. Statement of significance OXA could induce immunogenic cell death (ICD) via stimulating immune responses by increasing tumor cell stress and death, which triggers tumor-specific immune responses to achieve immunotherapy. How-ever, due to the insufficient Pt-DNA crosslinks, the ICD effect triggered by OXA cannot induce robust immune response. Mild hyperthermia has great potential to maximize the therapeutic outcome of ox-aliplatin by increasing the Pt-DNA cross-linking to augment the immunoresponse for enhanced cancer immunotherapy. (c) 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:198 / 210
页数:13
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