pH responsive coumarin and imidazole grafted polymeric micelles for cancer therapy

Polymer-small molecule conjugates could act as drug carriers to load hydrophobic antineoplastics by pi-pi in-teractions. However, weak hydrophobicity would lead to limited drug loading capacity and stability in blood circulation. Herein, we used the graft strategy to significantly increase the hydrophobicity for improving drug loading capacity and microenvironment stimuli characteristics. Coumarin and imidazole were grafted to bio-degradable and biocompatible poly(ethylene glycol)-b-poly(L-lysine) (PEG-PLL), respectively, endowing strong hydrophobicity for efficient drug loading and pH-responsiveness for controlled drug release. The critical micelle concentration of mPEG-PLL-g-COU/IMZ could be as low as 9.49 x 10(-6) mol/L. Anticancer drug doxorubicin (DOX) was used as a model drug and COU-grafted polymers showed high drug loading contents of similar to 17%. The pi-pi interactions between DOX and COU were established by UV and fluorescence spectroscopy. The pH-sensitive and COU-grafted polymeric micelles showed enhanced in vitro anticancer efficacy, due to the high drug loading capacity, faster cellular uptake, and pH-responsive drug release. This study indicated that stimuli-responsive, aromatic small molecule-grafted polymeric micelles could be a promising platform for efficient drug delivery and cancer therapy, due to their high drug loading capacity and controlled drug release.