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 pHsensitive 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. ARTICLE HISTORY

Engineered nanomedicines for tumor vasculature blockade therapy

“…In recent years, the targeted delivery of gene silencing agents through nanoparticles has become a key direction in the research of angiogenesis inhibition therapy for VEGF (J. Chen et al, 2017; Q. Chen et al, 2017; Di Paolo et al, 2011; Golkar, Samani, & Tamaddon, 2016; Guo, Yang, Jia, Moses, & Auguste, 2016; S. Huang et al, 2013; Lee et al, 2015; F. Li et al, 2019; Nagase, Hasegawa, Ayano, Maitani, & Kanazawa, 2019; Shi et al, 2017; Z. Yang et al, 2014; Z. Z. Yang, Li, Wang, Dong, & Qi, 2014; Yao, Wang, Liu, & Zhang, 2019; Q. Yu et al, 2014; Zhao et al, 2016). Small interfering RNA (siRNA) can be combined with the complementary region of the target gene transcription product messenger RNA to block the target gene at the RNA level.…”

Recent Advancements of Nanomedicine towards Antiangiogenic Therapy in Cancer

“…For example, Meneiand his team developed sorafenib-encapsulated lipid NPs for the treatment of glioblastoma, which showed high efficiency in the suppression of angiogenesis by inhibiting CD31 [88]. More recently, Zang and his group demonstrated that co-delivery of VEGF-siRNA and Sorafenib through pH-sensitive liposomes showed a synergistic effect in hepatocellular carcinoma [89]. Several other lipid-based NPs, along with other chemotherapeutics, are also being used for better antiangiogenic and antitumor therapy [90,91].…”

Recent Progress of Nanocarrier-Based Therapy for Solid Malignancies

“…Dual DDS is being investigated to deliver Sf, which is the only available systemic drug for HCC. The combined therapy of pH-sensitive carboxymethyl chitosan-coated liposomes for delivery of Sf and siRNA against vascular endothelial growth factor (VEGF-siRNA) was found to significantly enhanced VEGF downregulating effect, inducing cell early apoptosis, as compared to free siRNA and single loaded carrier [ 136 ].…”