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Author
Sánchez-Cortés Pedro, Andrea
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Abstract
Recently, many alternatives for gene delivery systems are emerging, be it with regard to encapsulation, the delivery method itself in the body, or the genetic material to be used. The main objective of these systems is the introduction of a gene to promote a therapeutic result and there are many different methods of distribution depending on the type of cells and tissues. This master's thesis proposes to study the intracellular processes of autophagy and ferritinophagy, which are involved in the internalization of polymeric nanoparticles. Currently, there are many studies regarding gene delivery systems, but in most, only the final results are observed, so we affirm that cells are black boxes, since not enough attention is paid to cellular processes.
In the first place, by means of OM-pBAE polyplexes, it will be investigated how the polymeric nanoparticles affect intracellular processes, by means of the LC3 (autophagy) and NCOA4 (ferritinophagy) proteins, both involved in the formation of the autophagosome where recycling will later take place. of damaged cell components. Second, the combination of these polymeric complexes with metallic nanoparticles called SPIONs will be studied, in terms of transfection efficiency and that they involve intracellularly. And finally, the effect of all cellular processes encapsulating pDNA, mRNA, and pure protein will be analyzed.
In conclusion, this project has used multicomponent nanoparticles to study the cellular mechanisms induced in cell transfection. Gene delivery systems have been used by polyplexes of OM-pBAE with pDNA, mRNA, and protein, as well as their combination with SPIONS. These compositions will allow us to analyze the intracellular processes - autophagy and ferritinophagia - and will shed light on the understanding between these processes and the internalization of nanoparticles.
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