Target delivery selective CSF-1R inhibitor to tumor-associated macrophages via erythrocyte-cancer cell hybrid membrane camouflaged pH-responsive copolymer micelle for cancer immunotherapy

• Published in: European journal of pharmaceutical sciences 2020-01, Vol.142, p.105136-105136, Article 105136
• Main Authors: Wang, Yuchi, Luan, Zhiyong, Zhao, Chaoyue, Bai, Chunhua, Yang, Kangjuan
• Format: Article
• Language: English
• Subjects: Dextran-grafted-poly (Histidine) Copolymer; Erythrocyte-cancer cell hybrid membrane; pH-responsive; Tumor immunotherapy; Tumor-associated macrophage (TAMs)
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2019.105136

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 (~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. [Display omitted]