The antitumor activity of
doxorubicin (DOX) is often limited owing to the occurrence of multidrug resistance (MDR) during treatment. Herein, we developed hybrid polymeric
micelles, which consisted of
pluronic F127 as long-circulating helper in blood, and phenylboronic
ester-grafted
pluronic P123 (PHE) as efflux and detoxification regulator to efficiently deliver DOX and reverse MDR in vivo. Hybrid
F127/PHE
micelles exhibited higher stability and drug encapsulation (~80%) than simple
F127/P123
micelles due to its lower CMC, and displayed in vitro drug release in a
hydrogen peroxide (H2O2)-sensitive manner. Besides, DOX-loaded hybrid
micelles (
F127/PHE-DOX) possessed higher cell-killing ability and induce more apoptotic in MDR-cells than other groups, which was probably because it not only could greatly increase intracellular drug concentration by inhibiting P-gp mediated drug efflux, but also promote
reactive oxygen species (ROS) generation by decreasing
glutathione (GSH) levels. Besides, in vivo evaluation indicated that
F127/PHE-DOX could well accumulate at
tumor regions and exhibit the strongest
tumor growth inhibition (TGI 87.87%) accompanied with low side effects. As a result,
F127/PHE
micelles had great potentials as a platform for anticancer drugs delivery and
tumor MDR reversal in clinical application.