Targeted delivery of docetaxel via Pi-Pi stacking stabilized dendritic polymeric micelles for enhanced therapy of liver cancer.

Delivery of taxane-based chemotherapeutics including Docetaxel (DTX) by conventional polymeric micelles still suffers from insufficient stability and rapid premature release during the circulation, which limits their targeting and anticancer efficiency. To conquer these challenges, we developed a novel DTX-loaded Pi-Pi stacking-stabilized dendritic polymeric micelle for targeted therapy of liver cancer. This dendritic polymeric micelle, referred to DPM-DTX-cRGD, was self-assembled from DTX and biodegradable dendritic block copolymers Poly(amidoamine)-poly(γ-benzyl-l-Glutamate)-b-polyethylene glycol-cRGD (PAM-PBLG-b-PEG-cRGD). DPM-DTX-cRGD held robust stability due to its covalent dendritic structure and would load abundant DTX with excellent retention via Pi-Pi stacking between DTX and the aromatic groups of the PBLG segments. The cellular uptake studies demonstrated that the cRGD-conjugated dendritic polymeric micelle (DPM) exhibited much higher cellular uptake in human liver cancer HepG2 cells than non-targeted DPM. The MTT assay also confirmed that DPM-DTX-cRGD caused much greater cytotoxicity than non-targeted DPM-DTX and a clinically available DTX formulation (Taxotere®). Therefore, this DPM-DTX-cRGD provides a novel attractive approach for targeted therapy of liver cancer.