Development of nanocarrier systems for breast cancer gene therapy medicinal products

Purpose: This study was performed to develop non-viral gene delivery systems with ideal properties for efficient and safe use in gene therapy as an alternative treatment in breast cancer. Methods: Nano sized vesicular systems which can deliver genes into breast cancer cells were prepared and their potential as a gene drug was assessed by investigating efficiency of gene delivery, toxicity, stability and hemolytic activity. ER (+), PR (+) and HER2 (-) MCF-7 human breast cancer cells were used as breast cancer cell lines. Results: Transfection of MCF-7 breast cells was achieved by the prepared niosomes. Polyplexes were prepared by complexing branched PEI with pDNA at a ratio of 1:1 (v:v). Polypexes were later complexed with niosomes to form niopolyplexes. Niosomes had a particle size of 51.89 nm and a zeta potential value of +28.3 mV. Niopolyplexes were non-toxic to normal breast cell line MCF-12A, but were toxic to MCF-7 breast cancer cells. Niopolyplexes were designed as an effiecient nucleic acid delivery system for MCF-7 breast cancer cells. Niosomes were stable at room temperature (25 °C) for 3 months with no changes in size, charge and morphological properties. Because of their hemolytic activity they should be delivered by other administration routes than intravenous delivery. Conclusion: Nanosized niopolyplexes are designed as suitable delivery systems for stable and efficient delivery of nucleic acids into MCF-7 breast cancer cells. They have the potential to be used as a delivery system for gene therapy medicinal products after preclinical and clinical studies. Key words: cancer, breast cancer, gene therapy, gene therapy medicinal products, niosome