Enhancing Targeted Therapy in Hepatocellular Carcinoma through a pH-Responsive Delivery System: Folic Acid-Modified Polydopamine-Paclitaxel-Loaded Poly(3-hydroxybutyrate--3-hydroxyvalerate) Nanoparticles.

Currently, there is an inherent contradiction between the multifunctionality and excellent biocompatibility of anticancer drug nanocarriers, which limits their application. Therefore, to overcome this limitation, we aimed to develop a biocompatible drug delivery system for the treatment of hepatocellular carcinoma (HCC). In this study, we employed poly(3-hydroxybutyrate--3-hydroxyvalerate) (PHBV) as the fundamental framework of the nanocarrier and utilized the emulsion solvent evaporation method to fabricate nanoparticles loaded with paclitaxel (PTX), known as PTX-PHBV NPs. To enhance the tumor-targeting capability, a dopamine self-polymerization strategy was employed to form a pH-sensitive coating on the surface of the nanoparticles. Then, folic acid (FA)-targeting HCC was conjugated to the nanoparticles with a polydopamine (PDA) coating by using the Michael addition reaction, resulting in the formation of HCC-targeted nanoparticles (PTX-PHBV@PDA-FA NPs). The PTX-PHBV@PDA-FA NPs were characterized and analyzed by using dynamic light scattering, scanning electron microscopy, fourier-transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. Encouragingly, PTX-PHBV@PDA-FA NPs exhibited remarkable anticancer efficacy in an HCC xenograft mouse model. Furthermore, compared to raw PTX, PTX-PHBV@PDA-FA NPs showed less toxicity in vivo. In conclusion, these results demonstrate the potential of PTX-PHBV@PDA-FA NPs for HCC treatment and biocompatibility.