Biointerface-Engineered Hybrid Nanovesicles for Targeted Reprogramming of Tumor Microenvironment
Title of Paper:
Biointerface-Engineered Hybrid Nanovesicles for Targeted Reprogramming of Tumor Microenvironment
Summary:
The tumor microenvironment (TME) of typical tumor types such as triple-negative breast cancer is featured by hypoxia and immunosuppression with abundant tumor-associated macrophages (TAMs), which also emerge as potential therapeutic targets for antitumor therapy. M1-like macrophage-derived exosomes (M1-Exos) have emerged as a promising tumor therapeutic candidate for their tumor-targeting and macrophage-polarization capabilities. However, the limited drug-loading efficiency and stability of M1-Exos have hindered their effectiveness in antitumor applications. Here, a hybrid nanovesicle is developed by integrating M1-Exos with AS1411 aptamer-conjugated liposomes (AApt-Lips), termed M1E/AALs. The obtained M1E/AALs are loaded with perfluorotributylamine (PFTBA) and IR780, as P-I, to construct P-I@M1E/AALs for reprogramming TME by alleviating tumor hypoxia and engineering TAMs. P-I@M1E/AAL-mediated tumor therapy enhances the in situ generation of reactive oxygen species, repolarizes TAMs toward an antitumor phenotype, and promotes the infiltration of T lymphocytes. The synergistic antitumor therapy based on P-I@M1E/AALs significantly suppresses tumor growth and prolongs the survival of 4T1-tumor-bearing mice. By integrating multiple treatment modalities, P-I@M1E/AAL nanoplatform demonstrates a promising therapeutic approach for overcoming hypoxic and immunosuppressive TME by targeted TAM reprogramming and enhanced tumor photodynamic immunotherapy. This study highlights an innovative TAM-engineering hybrid nanovesicle platform for the treatment of tumors characterized by hypoxic and immunosuppressive TME.
A nanoplatform combining M1-like macrophage-derived exosomes and AS1411 aptamer-modified liposomes is developed, as P-I@M1E/AALs, exhibiting enhanced cargo-loading capability and stability. P-I@M1E/AALs can effectively facilitate oxygen and photosensitizer delivery, achieving in situ engineering of tumor-associated macrophages and alleviation of tumor hypoxia. This approach reprograms tumor microenvironment and suppresses tumor growth, demonstrating a promising strategy for antitumor therapy. image
Co-author:
Zhe, Xueyan; L, Yongjiang; Y, Wanqing; Zha, Tingting; Li Min; Huang Jinhai; Kong Na; Xie Xiaoyu*; Wang Sicen*; Tao Wei*
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