Tumor-Homing and Immune-Reprogramming Cellular Nanovesicles for Photoacoustic Imaging-Guided Phototriggered Precise Chemoimmunotherapy

Many studies have focused on developing effective therapeutic strategies to selectively destroy primary tumors, eliminate metastatic lesions, and prevent tumor recurrence with minimal side effects on normal tissues. In this work, we synthesized engineered cellular nanovesicles (ECNVs) with tumor-hom...

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Bibliographic Details
Published in:ACS nano 2022-10, Vol.16 (10), p.16177-16190
Main Authors: Fan, Zhijin, Wang, Yichao, Li, Lanqing, Zeng, Fanchu, Shang, Qiuping, Liao, Yuhui, Liang, Changhong, Nie, Liming
Format: Article
Language:English
Subjects:
B7-H1 Antigen
CD8-Positive T-Lymphocytes
Cell Line, Tumor
Gold - pharmacology
Immunotherapy
Photoacoustic Techniques
Phototherapy
Tumor Microenvironment
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Summary:Many studies have focused on developing effective therapeutic strategies to selectively destroy primary tumors, eliminate metastatic lesions, and prevent tumor recurrence with minimal side effects on normal tissues. In this work, we synthesized engineered cellular nanovesicles (ECNVs) with tumor-homing and immune-reprogramming functions for photoacoustic (PA) imaging-guided precision chemoimmunotherapy. M1-macrophage-derived cellular nanovesicles (CNVs) were loaded with gold nanorods (GNRs), gemcitabine (GEM), CpG ODN, and PD-L1 aptamer. The good histocompatibility and tumor-homing effect of CNVs improved drug retention in the bloodstream and led to their enrichment in tumor tissues. Furthermore, the photothermal ability of GNRs enabled PA imaging-guided drug release. GEM induced tumor immunogenic cell death (ICD), and CpG ODN promoted an immune response to the antigens released by ICD, leading to long-term specific antitumor immunity. In addition, the PD-L1 aptamer relieved the inhibitory effect of the PD1/PD-L1 checkpoint on CD8+ T-cells and augmented the immunotherapeutic effect. The synergistic innate and adaptive immune responses enhanced the antitumor effect of ECNVs. In summary, this nanoplatform integrates local targeted photothermal therapy with extensive progressive chemotherapy and uses ICD to reshape the immune microenvironment for tumor ablation.
ISSN:1936-0851
1936-086X
DOI:10.1021/acsnano.2c04983