Pluronic-Based Nanoparticles for Delivery of Doxorubicin to the Tumor Microenvironment by Binding to Macrophages.

Abstract

The active targeting drug delivery system based on special types of endogenous cells such as macrophages has emerged as a promising strategy for tumor therapy, owing to its tumor homing property and biocompatibility. In this work, the active tumor-targeting drug delivery system carrying doxorubicin-loaded nanoparticles (DOX@MPF127-MCP-1, DMPM) on macrophage (RAW264.7) surfaces via the mediation of interaction with the CCR2/MCP-1 axis was exploited. Initially, the amphiphilic block copolymer Pluronic F127 (PF127) was carboxylated to MPF127 at the hydroxyl terminus. Subsequently, MPF127 was modified with MCP-1 peptide to prepare MPF127-MCP-1 (MPM). The DOX was wrapped in MPM to form DMPM nanomicelles (approximately 100 nm) during the self-assembly process of MPM. The DMPM spontaneously bound to macrophages (RAW264.7), which resulted in the construction of an actively targeting delivery system (macrophage-DMPM, MA-DMPM) <i>in vitro</i> and <i>in vivo</i>. The DOX in MA-DMPM was released in the acidic tumor microenvironment (TME) in a pH-responsive manner to increase DOX accumulation and enhance the tumor treatment effect. The ratio of MA-DMPM homing reached 220% <i>in vitro</i> compared with the control group, indicating that the MA-DMPM was excellently capable of tumor-targeting delivery. In <i>in vivo</i> experiments, nonsmall cell lung cancer cell (NCI-H1299) tumor models were established. The results of the fluorescence imaging system (IVIS) showed that MA-DMPM demonstrated tremendous tumor-targeting ability <i>in vivo</i>. The antitumor effects of MA-DMPM <i>in vivo</i> indicated that the proportion of tumor cell apoptosis in the DMPM-treated group was 63.33%. The findings of the tumor-bearing mouse experiment proved that MA-DMPM significantly suppressed tumor cell growth, which confirmed its immense potential and promising applications in tumor therapy.