Journal
MOLECULAR PHARMACEUTICS
Volume 16, Issue 4, Pages 1714-1722Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.9b00065
Keywords
tumor associated macrophages; tumor microenvironment; miR155; nanoparticles; tumor immunotherapy
Funding
- National Natural Science Foundation of China [81573370, 81872820]
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Tumor associated macrophages (TAMs) are important components residing in the tumor microenvironment. They are immunosuppressive and promote tumor progression. Targeting TAMs and reprogramming their phenotype may be a promising strategy that can restore antitumor immune responses. In this study, we developed a microRNA delivery system based on lipid-coated calcium phosphonate nanoparticles (CaP/miR@pMNPs) containing conjugated mannose and sterically shielded with a pH-responsive material. The nanocarrier could respond to the low pH in the tumor microenvironment and expose mannose to promote cellular internalization in TAMs. The carrier could reactivate TAMs and reprogram their functions, reverse the immunosuppressive tumor microenvironment, and inhibit tumor growth in a tumor-bearing mouse model. In summary, redirecting the polarization of TAMs is a potential therapeutic strategy for tumor immunotherapy.
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