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Methotrexate-plasmid DNA polyplexes for cancer therapy: Characterization, cancer cell targeting ability and tuned in vitro transfection

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Abstract Cell targeting is still the most auspicious task in the design/development of innovative drug and gene delivery systems for advanced biomedical applications. To evolve from conventional delivery vectors, which… Click to show full abstract

Abstract Cell targeting is still the most auspicious task in the design/development of innovative drug and gene delivery systems for advanced biomedical applications. To evolve from conventional delivery vectors, which present several limitations, we report a novel strategy combining a targeting tool associated with both chemical and gene therapies. To accomplish this innovation, the anti-cancer drug methotrexate (MTX) has been loaded into polyplexes based on polyethylenimine (PEI) and a p53 encoding plasmid DNA. The main properties (size, zeta potential, loading and complexation capacity) of the conceived triple-action vector have been determined and revealed to be adequate for intracellular applications. Furthermore, the fine structure of MTX/pDNA based carriers has been analysed by Fourier-transformed infrared (FTIR) spectroscopy. The cancer-cell targeting ability of the developed formulations has been evaluated. Studies on fibroblast and HeLa cells demonstrate the MTX cancer cell targeting through folate receptors, viewed as surface biomarkers and commonly overexpressed in tumors. This achievement supports the evidence for receptor mediated endocytosis. Confocal microscopy studies confirmed intracellular localization of targeting polyplexes, resulting in enhanced sustained pDNA uptake. Furthermore, the efficiency of in vitro transfection can be modulated by MTX concentration with great implications on gene expression and protein production. Preliminary assays on the treatment of cancer cells with the tri-functional PEI/pDNA/MTX vectors show a significant reduction of their viability.

Keywords: cell targeting; plasmid dna; cancer; cancer cell; targeting ability

Journal Title: Journal of Molecular Liquids
Year Published: 2019

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