Mitochondria-targeted photothermal-chemodynamic therapy enhances checkpoint blockade immunotherapy on colon cancer

被引：0
作者：
Zheng, Benchao [1 ,2 ]
Wang, Hongbo [1 ,2 ]
Zhai, Shiyi [1 ,2 ]
Li, Jiangsheng [3 ]
Lu, Kuangda [1 ,2 ]
机构：
[1] Peking Univ, Inst Med Technol, Hlth Sci Ctr, Beijing 100191, Peoples R China
[2] Peking Univ, Inst Adv Clin Med, Beijing 100191, Peoples R China
[3] Peking Univ Canc Hosp, Dept Nucl Med, Key Lab Carcinogenesis & Translat Res, Minist Educ,Key Lab Res & Evaluat Radiopharmaceut, Beijing 100142, Peoples R China
来源：
MATERIALS TODAY BIO | 2025年 / 31卷
基金：
中国国家自然科学基金;
关键词：
Mitochondria-targeting; Photothermal therapy; Chemodynamic therapy; Checkpoint blockade immunotherapy; Cancer;
D O I：
10.1016/j.mtbio.2025.101542
中图分类号：
R318 [生物医学工程];
学科分类号：
0831 ;
摘要：
Immunotherapy has emerged as a hotspot for cancer treatment. However, the response rate of monotherapy remains relatively low in clinical settings. Photothermal therapy (PTT), which employs light energy to ablate tumors, can also activate tumor-specific immune responses. This effect has been attributed in several studies to the release of damage-associated molecular patterns (DAMPs) triggered by mitochondrial injury. We propose that mitochondria-targeted PTT may better synergize with immunotherapy. Herein, we constructed a multifunctional nanoplatform that enables mitochondria-targeted photothermal-chemodynamic combination therapy by conjugating indocyanine green-thiol (ICG-SH) and mercaptoethyl-triphenylphosphonium (TPP-SH) onto polyvinyl pyrrolidone (PVP)-coated gold-copper nanoparticles (AIT). Upon near-infrared light (NIR) irradiation, AIT ablates cancer cells and amplifies the effect of chemodynamic therapy (CDT), thereby inducing apoptosis in the tumor. The combination of CDT and PTT promotes immunogenic cell death, which could synergize with checkpoint blockade immunotherapy. In a bilateral mouse colon cancer model, we observed complete eradication of light-irradiated primary tumors and significant inhibition of distant untreated tumors in the group treated with AIT plus anti-PD-1 (alpha PD-1). We found a significant increase in serum levels of pro-inflammatory factors, including interleukin-6 (IL-6), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha), following PTT/CDT/immunotherapy treatment, suggesting effective activation of the immune response. The enhanced immunogenicity caused by AIT with alpha PD-1 treatment resulted in efficient antigen presentation, as indicated by the increased infiltration of dendritic cells (DCs) into the tumor-draining lymph nodes (LNs). We also observed enhanced infiltration of CD8+ T cells in distant tumors in the AIT with alpha PD-1 group compared to alpha PD-1 alone. Hence, mitochondria-targeting represents an effective strategy to potentiate the combination of photothermal, chemodynamic, and immune checkpoint blockade therapies for the treatment of metastatic cancer.
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页数：13
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