Finding the ideal polyethylenimine-plasmid DNA system for co-delivery of payloads in cancer therapy

Researchers still hold for the development of a safety and advanced delivery system able of efficient therapeutic action. The co-delivery of different payloads is part of this strategy and has already demonstrated to be a valuable tool against the most severe diseases. In the pursuit of an "ideal" drug/gene co-delivery vector for cancer therapy, we present a complete comparison study of different morphology and molecular weight polyethylenimine (PEI)/p53 encoding plasmid DNA (pDNA) polyplexes. Besides pDNA, also methotrexate (MTX) has been loaded into PEI/pDNA nanoparticles. The polyplexes have been characterized in terms of morphology, size, surface charges, loading/encapsulation efficiencies and toxicity. Although the nature of PEI can influence these properties, they deeply vary with the polymer nitrogen to pDNA phosphate (N/P) ratio. The transfection of HeLa cells mediated by PEI/pDNA/MTX vectors leads to both the release of MTX and the p53 protein expression. Modelling of MTX release kinetics brings valuable information concerning drug delivery mechanism. Moreover, the success of transfection is dependent on the nature of PEI and, mainly, on the N/P ratio used in the formulation of polyplexes. This work represents a great contribution for the design and development of innovative PEI based carriers for the most challenging biomedical applications.