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Acidity-activatable dynamic hybrid nanoplatforms derived from extracellular vesicles of M1 macrophages enhance cancer immunotherapy through synergistic triple immunotherapy

Authors :
Yawen Guo
Tingting Lv
Zijie Li
Xin Wei
Chunwang Yang
Wen Li
Xiaoming Hou
Zhiyu Wang
Ruijie Qian
Source :
Journal of Nanobiotechnology, Vol 22, Iss 1, Pp 1-20 (2024)
Publication Year :
2024
Publisher :
BMC, 2024.

Abstract

Abstract Immunotherapy exhibits considerable promise for sustained tumor reduction. However, current cancer immunotherapy methods elicit limited responses due to the inadequate immunogenicity exhibited by cancer cells. This obstacle may be addressed using nanoplatforms that can activate synergistic therapies (photodynamic therapy and ferroptosis) in response to the acidic pH of the tumor microenvironment. We previously developed an amphiphilic photosensitizer, SR780, which displays satisfactory photodynamic effects. This photosensitizer is inactivated when bound to Fe3+ (SR780Fe) but is activated upon release in mildly acidic conditions. In this study, M1 macrophage-derived extracellular vesicles (EVs) were fused with REV and SR780Feā€“loaded liposomes (REV@SR780Fe@Lip) to form REV@SR780Fe@LEV hybrid nanovesicles. Further modification with the RS17 peptide for tumor targeting enabled a combination of photodynamic therapy, ferroptosis, and cGAS-STING pathway activation, resulting in enhanced antitumor efficacy through a synergistic effect. Upon laser irradiation, REV@SR780Fe@LEV-RS17 demonstrated antitumor effects in 4T1 breast cancer models, including the inhibition of lung and liver metastasis, as well as prevention of tumor recurrence. Graphical Abstract

Details

Language :
English
ISSN :
14773155
Volume :
22
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Journal of Nanobiotechnology
Publication Type :
Academic Journal
Accession number :
edsdoj.b67a7051570a4a809c27acd175d970b3
Document Type :
article
Full Text :
https://doi.org/10.1186/s12951-024-02719-7