Novel multi-targeted nanoparticles for targeted co-delivery of nucleic acid and chemotherapeutic agents to breast cancer tissues

摘要

Selective delivery of drugs to damaged tissues favorable to reduce the side effects while enhancing the therapeutic efficacy. The purpose of the present study was the design and synthesis of multi-targeted nanoparticles for co-delivery of both drug and nucleic acid to cancer cells. In this study biocompatible compounds such as chitosan, polyethylene glycol (PEG), polycaprolactone (PCL), folic acid (FA) and glucose (Glu) were used to synthesize the FA-PEG-Chitosan-PCL-Chitosan-PEG-FA (FPCP) and Glu-PEG-Chitosan-PCL-Chitosan-PEG-Glu (GPCP) copolymers. Then, paclitaxel (PTX), oleic acid-coated FeCO nanoparticles (FeCO-OA) and 6-carboxy-fluorescein phosphoramidate (FAM)-labeled siRNA (siRNA-FAM) were encapsulated into either FPCP or GPCP, or both FPCP and GPCP (GFPCP), using the solvent evaporation technique.In vitro and in vivo biocompatibility and drug delivery efficiency of FPCP/FeCO-OA/PTX, GPCP/FeCO-OA/PTX and GFPCP/FeCO-OA/PTX nanoparticles were determined by recording the MTT assay, weight loss and tumor volume respectively. In addition, the ability of FPCP/FeCO-OA/siRNA-FAM, GPCP/FeCO-OA/siRNAFAM, and GFPCP/FeCO-OA/siRNA-FAM gene transfer was determined using flow cytometry analysis. Moreover, the effects of applying an external magnetic field to the tumor site on the efficiency of drug delivery using FPCP/FeCO-OA/siRNA-FAM/PTX (NPsA), GPCP/FeCO-OA/siRNA-FAM/PTX (NPsB) and GFPCP/FeCO-OA/siRNAFAM/PTX (NPsAB) were also investigated in the present study.No significant toxicity was observed for the FPCP and GPCP copolymers. Meanwhile, PTX encapsulated FPCP, GPCP and GFPCP exhibited greater anticancer activities against MCF-7 cells. The in vivo and in vitro results showed that the nanoparticles targeted with both folic acid and glucose increased drug and RNA transfer efficiency compared to when folic acid or glucose alone used. Also, the efficiency of PTX and siRNA-FAM delivery to tumor tissues by nanoparticles increased significantly by applying an external magnetic field to the tumor area. The hydrophobic interactions between different amphipathic copolymers in appropriate is an efficient and easy technique to synthesize complex and multifunctional nanoparticles.