Hepatocellular carcinoma （HCC） is one of the major causes of death worldwide. Targeted delivery of drugs to tumor cells can be achieved by introduction of a targeting ligand onto the nanocarrier system. Simultaneous delivery of a chemotherapeutic drug and siRNA in one nanocarrier system to the tumor is a promising strategy for cancer treatment. In this study, we prepared cationic liposomes to co-deliver docetaxel （DTX） and small interfering RNA （siRNA）. The liposomes were modified by a hepatocellular carcinoma specific homing peptide, SP94. Serum stability assay demonstrated that liposomes can significantly protect the siRNA against enzymatic degradation in serum. The SP94 modified liposomes showed increased cellular uptake and stronger anti-tumor effect compared with the unmodified liposomes on human HCC cells. The data indicated that the SP94 modified liposomes which co-deliver DTX and siRNA could be used for the targeted therapy of hepatocellular carcinoma.
Surface modification may have important influences on the penetration behavior of nanoscale drug delivery system. In the present study, we mainly focused on whether cell targeting or cell penetration could affect penetration abilities of nanostructured lipid carriers（NLC）. Real--time penetration of folate--or cell penetrating peptide（CPP）-modified NLC was evaluated using a multicellular tumor spheroid（MTS） established by stacking culture method as an in vitro testing platform. The results suggested that CPP modification had a better penetration behavior both on penetration depth and intensity compared with folate-modified NLC at the early stage of penetration process.
It is a promising treatment strategy to use a nanoparticle-based drug delivery system for cancer patients, which can simultaneously deliver multiple drugs or genes in combination with therapy to induce synergistic effects and suppress drug resistance to the tumor. In this study, cationic nanostructured lipid carriers（cNLC） for co-loading anionic small-interfering RNAs（siRNA） and chemotherapeutic docetaxel（DTX） were prepared from different cationic lipids based on particle distribution and loading efficiency. In order to increase the cNLC＇s positive targeting capacity, a novel peptide SP94 was bound to the surface of cNLC（SP94-cNLC）. The cNLC showed good efficiency in loading siRNA and DTX. The SP94-cNLC revealed a better cytotoxicity compared with cNLC and Taxotere？, indicating that SP94 could successfully enhance the internalization capacity of nanoparticles to the liver cancer cells. This new type of cNLC is a potential vehicle when using in co-delivery of chemotherapeutics and siRNAs. The curcumin（CUR）/DTX co-delivery NLC could load both CUR and DTX in high efficiency and showed a sensibilization to DTX chemotherapy. The sensibilization was more obvious when it was used in the aggressive and resistant cancer cells. This CUR/DTX co-delivery system had good potential in treating cancer cells when chemotherapy drug showed little effect alone.
