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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, the present study tried to incorporate siRNA and paclitaxel (PTX) simultaneously into a novel nanocarrier. The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid (FA) and glucose (Glu) onto its surface. The structure of nanocarrier was formed from ternary magnetic copolymers based on FeCo-polyethyleneimine (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 significant anticancer activity against MCF-7 and BT-474 cell lines. NPsAB/siRNA/PTX nanoparticles showed greater effects on MCF-7 and BT-474 cells viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX. Also, they induced significantly higher anticancer effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using FA and Glu. We concluded that NPsAB nanoparticles have a great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy.

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Cationic polyamidoamine (PAMAM) dendrimers are highly branched nanoparticles with unique molecular properties, which make them promising nanocarriers for gene delivery into cells. This research evaluated the ability of hyperbranched PAMAM (hPAMAM)-G2 with a diethylenetriamine core to interact with DNA, its protection from ultrasonic damage, and delivery to alfalfa cells. Additionally, the effects of ultrasound on the efficacy of hPAMAM-G2 for the delivery and expression of the gusA gene in the alfalfa cells were investigated. The electrophoresis retardation of plasmid DNA occurred at an N/P ratio (where N is the number of hPAMAM nitrogen atoms and P is the number of DNA phosphorus atoms) of 3 and above, and hPAMAM-G2 dendrimers completely immobilized the DNA at an N/P ratio of 4. The analysis of the DNA dissociated from the dendriplexes revealed a partial protection of the DNA from ultrasound damage at N/P ratios lower than 2, and with increasing N/P ratios, the DNA was better protected. Sonication of the alfalfa cells in the presence of ssDNA-FITC-hPAMAM increased the ssDNA delivery efficiency to 36%, which was significantly higher than that of ssDNA-FITC-hPAMAM without sonication. Additionally, the efficiency of transfection and the expression of the gusA gene were dependent on the N/P ratio and the highest efficiency (1.4%) was achieved at an N/P ratio of 10. The combination of 120 s of ultrasound and hPAMAM-DNA increased the gusA gene transfection and expression to 3.86%.