Abstract 303: Surface modification of paclitaxel-loaded nanoparticles based on polydopamine with pH sensitive property for targeted therapy in hepatocellular carcinoma

Abstract

Drug-loaded nanocarrier is a promising treatment for targeted therapy in hepatocellular carcinoma (HCC) due to their sustained release and outstanding tumor-targeting properties. Nevertheless, a limitation of current nanocarriers is the contradiction between multiple functions and favorable biocompatibility, owing to most of functional substances are non-biological. In this study, we introduced a targeting arginine-glycine-aspartic acid (RGD)-peptide on the surface of polydopamine (PDA)-ploy (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) to develop a novel nanoparticle, which were employed as a drug delivery system loaded with paclitaxel (PTX) for HCC therapy. Paclitaxel-loaded PHBV nanoparticles (PHBV-PTX-NPs) were prepared by emulsion solvent evaporation. As a gatekeeper, the pH-sensitive coating was formed by self-polymerization of dopamine. The RGD and PDA coated nanoparticles were combined through the Michael addition. The chemical structures and properties of these nanoparticles were characterized by dynamic light scattering-autosizer, transmission electron microscope, fourier transform infrared spectroscopy, differential scanning calorimetry, thermogravimetry and X-ray photoelectron spectroscopy. As expected, these RGD-PDA-PHBV-PTX-NPs achieved excellent targeting efficiency, which was revealed by the cellular uptake and cytotoxicity assay in HCC cells. Compared with that of free PTX, the RGD-PDA-PHBV-PTX-NPs showed more superior antitumor efficacy in the xenograft mouse model. Notably, in addition to efficient anticancer activities, RGD-PDA-PHBV-PTX-NPs exhibited lower toxicity than PTX to normal hepatocytes and mouse in vitro and in vivo, respectively. These studies suggest the potential beneficial use of RGD-PDA-PHBV-PTX-NPs in future HCC-targeted therapy with drug-loaded nanocarriers. Citation Format: Mingfang Wu, Xinming Xia, Danna Sun, Chen Zhong. Surface modification of paclitaxel-loaded nanoparticles based on polydopamine with pH sensitive property for targeted therapy in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 303.