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Autophagy activator-loaded bicomponent peptide nanocarriers for phototherapy-triggered immunity enhancement against metastatic breast cancer

Mild autophagy accompanied with immunogenic cell death (ICD) effect destructs immune-associated antigens, weakening the immune response against tumor growth. To address this dilemma, we develop a peptide-based bicomponent nanocarrier with encapsulation of a cellular hyperautophagy activator (STF-622...

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Bibliographic Details
Published in:Journal of controlled release 2024-12, Vol.376, p.241-252
Main Authors: Ma, Teng, Li, Danqi, Yang, Zhuo-Ran, Wang, Qi, Chen, Rong, Lv, Niannian, Du, Kehan, Qin, Huimin, Tao, Juan, Jiang, Hao, Zhu, Jintao
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Language:English
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Summary:Mild autophagy accompanied with immunogenic cell death (ICD) effect destructs immune-associated antigens, weakening the immune response against tumor growth. To address this dilemma, we develop a peptide-based bicomponent nanocarrier with encapsulation of a cellular hyperautophagy activator (STF-62247) for near-infrared (NIR) photo/immunotherapy to eliminate primary and metastatic breast tumors. The electrostatic-driven nanodrug (PPNPs@STF) with active-targeting and efficient endosomal escape can induce specific ICD effect upon NIR laser irradiation, and trigger autophagy to a mild activation state. Notably, the simultaneously released STF-62247 precisely promotes autophagy to an overactivated state, resulting in autophagic death of tumor cells and further boosting ICD-related antigen presentation. More importantly, the combined photo/immunotherapy of PPNPs@STF not only inhibits tumor cell proliferation, but also promotes dendritic cells (DCs)-associated immune response. In 4 T1 tumor-bearing mice, PPNPs@STF effectively inhibits growth of primary and distant tumors, and suppresses lung metastasis with a minimized side effect. This study provides a hyperautophagy activator-assisted strategy that can enhance ICD-based antitumor immune response for the treatment of metastatic breast cancer. [Display omitted]
ISSN:0168-3659
1873-4995
1873-4995
DOI:10.1016/j.jconrel.2024.10.009