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Gold Nanoparticles as mRNA Delivery Vehicles in the context of Vaccines and Advanced Therapies

Abstract

Gold nanoparticles (AuNPs) have a wide potential for pharmaceutical application due to their biocompatibility, stability and ease surface modification in order to couple a variety of therapeutic molecules. Furthermore, the shape and size of AuNPs can be customized for specific biomedical applications, given that the physicochemical properties of these particles differ according to their morphology. One of these potential applications is the delivery of nucleic acids in advanced vaccines, a topic that has being attracting the attention of the scientific community. However, the synthesis of AuNPs with different sizes and shapes requires knowledge and complex process tuning. In this context, microfluidic systems present precise control of the reaction conditions, being able to offer a solution for the controlled and reproducible production of AuNPs. Therefore, the objective of this work is to study the controlled and reproducible synthesis of AuNPs that present different physicochemical characteristics in view of the functionalization with messenger RNAs (mRNAs) aiming at the development of new vaccine platforms. The synthesis of AuNPs in conventional and microfluidic reactors will be studied and the influence of different process parameters (reactant concentration, temperature, residence time and reactor characteristics) on the size, surface charge and shape of nanoparticles will be evaluated. The AuNPs produced will then be functionalized/complexed with different model mRNAs, capable of expressing reporter proteins (GFP and Luciferase), and the AuNP+mRNA complexes will be characterized and tested for stability, cytotoxicity and biological functionality, through transfection of mammalian cells. It is expected, therefore, the development of a new and efficient platform for the delivery of mRNA, capable of being used in new vaccines based on this technology. (AU)

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