Ultrasonic-Responsive Pluronic P105/F127 Nanogels for Overcoming Multidrug Resistance in Cancer

Effective management of multidrug-resistant cancers depends on effective, localized drug release and accumulation within the tumor microenvironment. In our work, Pluronic P105 and F127 mixed nanogels (PM) were fabricated through self-assembly to combat multidrug-resistant cancer. The approximate diameter of our prepared PM is 115.7 nm, an optimal size for tumor accumulation through the enhanced permeability and retention (EPR) effect. An in vitro drug release assay indicated that ultrasound could accelerate the drug release rate in doxorubicin-loaded Pluronic nanogels (PM/D). Additionally, the resistance reversion index (RRI) in the ultrasound-treated PM/D group was 4.55 and was two times higher than that in the free PM/D group, which represented better MDR reverse performance. Cell experiments demonstrated that, after 3 min of ultrasound, a greater amount of chemo-drug was released and absorbed by the MDR human breast cell line (MCF-7/ADR), resulting in significant cytotoxicity. Such enhanced therapeutic efficiency could be attributed to the combined effects of the two independent mechanisms: (i) ultrasound-controllable drug release realized effective release within resistant tumors with spatial and temporal precision and (ii) the contained Pluronic in the PM/D inhibited P-gp-mediated efflux activity to overcome MDR in tumors. Collectively, our findings support the feasibility of ultrasound-responsive PM as a drug-delivery platform for resistant cancers.