期刊
CHEMICAL ENGINEERING JOURNAL
卷 424, 期 -, 页码 -出版社
ELSEVIER SCIENCE SA
DOI: 10.1016/j.cej.2021.130171
关键词
Native mitochondrial targeting; Photothermal therapy; Immunotherapy; Immune checkpoint blockade; Tumor recurrence and metastasis
资金
- National Natural Scientific Foundation of China [51973071]
- Pearl River Young Talents Program of Science and Technology in Guangzhou [201906010047]
- Science and Technology Program of Guangzhou [2019050001]
- National Key Research and Development Program of China [2017YFA0205200, 2018YFA0209800]
This study introduces a novel immunomodulator nanoparticle that targets tumor cell mitochondria, combined with photothermal therapy and immune checkpoint blockade to enhance antitumor immune response, effectively suppressing tumor recurrence and metastasis.
Photothermal therapy (PTT) is a promising therapeutic modality, but still faces some potential limitations, such as unfavorable thermal damage to normal tissues, limited light penetration depth, unpredictable tumor recurrence and metastasis. Additionally, mitochondria play a key role in maintaining multiple cellular functions, whereas displaying fragile thermal sensitivity. Herein, we report on the fabrication of an immunomodulator (R848)-loaded polymeric nanoparticles, R848@cRGD-PDCS, which can spontaneously target mitochondria of tumor cells that benefits from native mitochondria-targeting near-infrared (NIR) light-absorbing moieties. Upon NIR laser irradiation, photothermal-induced mild hyperthermia can efficiently damage the mitochondria in primary tumor cells, promoting efficient release of tumor-associated antigens. Combined with the immune checkpoint blockade (ICB), tumor-mediated immunosuppression can be alleviated, thus the activated antitumor immune response can effectively suppress distant tumors and overcome tumor recurrence and metastasis, achieving long-term antitumor immune memory to inhibit tumor metastasis. Current native mitochondrial targeting phototherapeutic nanoparticles potentiated with immunotherapy are promising for precision translational medicine.
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