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

• Published in: ACS nano 2024-06, Vol.18 (22), p.14441-14456
• Main Authors: Hu, Chengrui, Wang, Jun, Gao, Xinxing, Xia, Jie, Li, Wanzhen, Song, Ping, Zhang, Weiwei, Ge, Fei, Zhu, Longbao
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - pharmacology; Chemokine CCL2 - metabolism; Doxorubicin - administration & dosage; Doxorubicin - chemistry; Doxorubicin - pharmacology; Drug Carriers - chemistry; Drug Delivery Systems; Humans; Macrophages - drug effects; Macrophages - metabolism; Mice; Mice, Inbred BALB C; Nanoparticles - chemistry; Poloxamer - chemistry; RAW 264.7 Cells; Tumor Microenvironment - drug effects
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/acsnano.4c01120

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) in vitro and in vivo. 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% in vitro compared with the control group, indicating that the MA-DMPM was excellently capable of tumor-targeting delivery. In in vivo 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 in vivo. The antitumor effects of MA-DMPM in vivo 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.