Design and preparation of a new multi-targeted drug delivery system using multifunctional nanoparticles for co-delivery of siRNA and paclitaxel
Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, it was tried to incorporate siRNA and paclitaxel simultaneously into a novel nanocarrier. The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid (FA) and glucose onto its surface. The structure of nanocarrier formed from ternary magnetic copolymers based on FeCo-polyethylenimine (FeCo-PEI) nanoparticles and polylactic acid-polyethylene glycol (PLA-PEG) gene delivery system. Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA), FeCo-PEI-PLA-PEG-Glu (NPsB) and FeCo-PEI-PLA-PEG-FA/Glu (NPsAB) nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay. Besides, siRNA-FAM internalization was investigated by fluorescence microscopy. The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations. Meanwhile, siRNA-FAM/PTX encapsulated nanoparticles exhibited greater cytotoxicity on MCF-7 cells. NPsAB/siRNA/PTX nanoparticles showed greater effect on MCF-7 cell viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX. Also, they induced significantly higher cytotoxic effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using folic acid and glucose. We concluded that NPsAB nanoparticles have great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy.