pH-responsive delivery vehicle based on RGD-modified polydopamine-paclitaxel-loaded poly (3-hydroxybutyrate-co-3-hydroxyvalerate) nanoparticles for targeted therapy in hepatocellular carcinoma

Abstract A limitation of current anticancer nanocarriers is the contradiction between multiple functions and favorable biocompatibility. Thus, we aimed to develop a compatible drug delivery system loaded with paclitaxel (PTX) for hepatocellular carcinoma (HCC) therapy. A basic backbone, PTX-loaded poly (3-hydroxybutyrate-co-3-hydroxyvalerate) PHBV nanoparticle (PHBV-PTX-NPs), was prepared by emulsion solvent evaporation. As a gatekeeper, the pH-sensitive coating was formed by self-polymerization of dopamine (PDA). The HCC-targeted arginine-glycine-aspartic acid (RGD)-peptide and PDA-coated nanoparticles (NPs) were combined through the Michael addition. Subsequently, the physicochemical properties of RGD-PDA-PHBV-PTX-NPs were characterized by dynamic light scattering-autosizer, transmission electron microscope, fourier transform infrared spectroscopy, differential scanning calorimetry, thermogravimetry and X-ray spectroscopy. As expected, the RGD-PDA-PHBV-PTX-NPs showed robust anticancer efficacy in a xenograft mouse model. More importantly, they exhibited lower toxicity than PTX to normal hepatocytes and mouse in vitro and in vivo, respectively. Taken together, these results indicate that the RGD-PDA-PHBV-PTX-NPs are potentially beneficial for easing conflict between multifunction and biocompatible characters of nanocarriers.