Journal
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 142, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ejps.2019.105136
Keywords
Tumor immunotherapy; Tumor-associated macrophage (TAMs); Dextran-grafted-poly (Histidine) Copolymer; Erythrocyte-cancer cell hybrid membrane; pH-responsive
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Tumor-associated macrophages (TAMs) is a promising therapeutic target for cancer immunotherapy, while TAMs targeting therapy using nano-sized drug delivery system (NDDS) is a great challenge. To overcome these drawbacks, a novel erythrocyte-cancer cell hybrid membrane camouflaged pH-responsive copolymer micelle (dextran-grafted-poly (histidine) copolymer) was prepared to target deliver a selective CSF-1R inhibitor: BLZ-945 (shorten as DH@ECm) to TAMs for TAMs depletion. The prepared DH@ECm possessed favorable particle size (similar to 190 nm) preferable immune camouflage and tumor homologies targeting characteristic when it was intravenously administrated into blood system. In tumor acidic microenvironment, DH@ECm possessed pH-responsive characteristic and unique membrane escape effect to facilitate recognition and internalization by TAMs via dextran-CD206 receptor specific interaction (about 3.9 fold than free drug), followed by TAMs depletion in vitro. For in vivo studies, DH@ECm could reverse tumor immune-microenvironment with the elevation of CD8(+) T cells and possess sufficient tumor immunotherapy (inhibition rate: 64.5%). All the in vitro and in vivo studies demonstrated the therapeutical potential of DH@ECm for tumor immunotherapy.
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