Abstract
Biocompatible, pH-sensitive and charge-conversion micelles derived from hyaluronic acid (HA), poly(lactide) (PLA) and half-generation of sectorial poly(amidoamine) dendrimers (sPA G4.5) were designed and fabricated to target delivery of docetaxel (DTX) to cancer cells. The novel micelles (HA-PALA-DTX) possessed stability against rat plasma and were capable of reversing surface zeta potential under acidic conditions in the presence of HAase. Moreover, the blank micelles demonstrated satisfactory biocompatibility and viability for biomedical applications. A cellular internalization experiment indicated that HA played an important role in increasing intracellular accumulation of DTX delivered by the micelles. Compared to Taxotere® and PALA-DTX, HA-PALA-DTX showed an enhanced anticancer activity in vivo, with a tumor growth inhibition rate of 72.32 ± 5.22%. Overall, the functionalized micelles could be utilized as an alternative carrier for effective targeted delivery of anticancer agents to improve therapeutic efficacy and minimize adverse effects.
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