Multi-functionalized dendrimers for targeted co-delivery of sorafenib and paclitaxel in liver cancers

Liver cancer is one of the leading causes of cancer mortality worldwide. In this study, poly(lactide) (PLA) and hyaluronic acid (HA) co-modified half-generation of PAMAM G4.5 dendrimers (sPA) was chosen as the intelligent carrier for co-delivery of paclitaxel (PTX) and sorafenib (SOR) to treat liver cancer. The multifunctional micelle (HA-PALA@PTX + SOR) possessed a uniform size of 152.6 nm, good stability against serum medium, and a rapid in vitro drug release behavior under acidic condition in the presence of HAase. Cellular uptake study demonstrated an efficient intracellular delivery and drug accumulation in HepG2 cells. The antitumor and anti-metastasis efficacy of functionalized micelle was more obvious than that of free drugs. These data provided strong evidence that HA-PALA@PTX + SOR micelle could be utilized as a biocompatible and tumor targeted nano-carrier for the delivery of multiple anticancer drugs in liver cancer treatment.