Journal
BIOMACROMOLECULES
Volume 19, Issue 6, Pages 2146-2155Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.biomac.8b00239
Keywords
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Funding
- National Natural Science Foundation of China [81371679, 81701816, 81671758, 31571013, 51502333, 81501580]
- Key International S&T Cooperation Project [2015DFH50230]
- Natural Science Foundation of Guangdong Province [2017A030313079, 2017A030313726]
- Guangdong Natural Science Foundation of Research Team [2016A030312006]
- Shanghai Science and technology Program [16DZ1910900]
- Dongguan Project on Social Science and Technology Development [2015108101019]
- Shenzhen Science and Technology Program [JSGG20160331185422390, JCYJ20160429191503002]
- China Postdoctoral Science Foundation [2017M612776]
- SIAT Innovation Program for Excellent Young Researchers [Y7G005]
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One approach to cancer immunotherapy is the repolarization of immunosuppressive tumor-associated macrophages (TAMs) to antitumor M1 macrophages. The present study developed galactose-functionalized zinc protoporphyrin IX (ZnPP) grafted poly(L-lysine)-b-poly(ethyleneglycol) polypeptide micelles (ZnPP PM) for TAM-targeted immunopotentiator delivery, which aimed at in vivo repolarization of TAMs to antitumor M1 macrophages. The outcomes revealed that ROS-inducing ZnPP PM demonstrated specificity for the in vitro and in vivo targeting of macrophages, elevated the level of ROS, and lowered STAT3 expression in BM-TAMs. Poly I:C (PIC, a TLR3 agonist)-loaded ZnPP PM (ZnPP PM/PIC) efficiently repolarized TAMs to M1 macrophages, which were reliant on ROS generation. Further, ZnPP PM/PIC substantially elevated the activated NK cells and T lymphocytes in B16-F10 melanoma tumors, which caused vigorous tumor regression. Therefore, the TAM-targeted transport of an immunologic adjuvant with ZnPP-grafted nanovectors may be a potential strategy to repolarize TAMs to Ml macrophages in situ for effective cancer immunotherapy.
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