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RGD peptide targeted lipid-coated nanoparticles for combinatorial delivery of sorafenib and quercetin against hepatocellular carcinoma

Abstract Context: Combination therapies provide a potential solution to address the tumor heterogeneity and drug resistance issues by taking advantage of distinct mechanisms of action of the multiple therapeutics. Objective: To design arginine-glycineaspartic acid (RGD) modified lipid-coated nanoparticles (NPs) for the co-delivery of the hydrophobic drugs against hepatocellular carcinoma (HCC). Materials and methods: RGD modified lipid-coated PLGA NPs were developed for the targeted delivery of both sorafenib (SRF) and quercetin (QT) (RGD-SRF-QT NPs). Chemical–physical characteristics and release profiles were evaluated. In vitro cell viability assays were carried out on HCC cells. In vivo antitumor efficacies were evaluated in HCC animal model. Results and discussion: The combination of SRF and QT formulations was more effective than the single drug formulations in both NPs and solution groups. RGD-SRF-QT NPs achieved the most significant tumor growth inhibition effect in vitro and in vivo. Conclusion: The resulting NPs could provide a promising platform for co-delivery of multiple anticancer drugs for achievement of combinational therapy and could offer potential for enhancing the therapeutic efficacy on HCC.