Co-delivery of sorafenib and VEGF-siRNA via pH-sensitive liposomes for the synergistic treatment of hepatocellular carcinoma

Abstract

Non-viral nanocarrier affords a platform for drug and siRNA combination, the focus of which is to load drug and siRNA into a single carrier, allowing for co-delivery and a synergistic effect at tumour site. In our previous study, pH-sensitive carboxymethyl chitosan-modified liposomes (CMCS-SiSf-CL) were assembled for sorafenib (Sf) and Cy3-siRNA co-loaded. The present study evaluated in vitro and in vivo co-delivery of the co-loaded liposomes. Further, in vitro inhibiting hepatocellular carcinoma of the pH-sensitive sorafenib (Sf) and VEGF-siRNA co-loaded liposomes was discussed. The experimental results demonstrated co-delivery and penetration into 2-dimensional (2D) cultured HepG2 cells, 3-dimensional (3D) cultured HepG2 tumour spheroids and tumour regions of H22 tumour-bearing mice. Compared with free siRNA and single loaded carrier, co-delivery liposomes exhibited enhanced VEGF downregulating effect, inducing cell early apoptosis. Therefore, the CMCS-SiSf-CL delivery system can lay the foundation for the co-delivery systems development and provide new area for HCC therapy.