Nanoparticles are promising structures for the development of diagnostic and therapeutic agents. On the other hand, despite the great potential, the current stage of nanoparticles application in the biomedical field is followed by a low therapeutic efficacy, less than 1 %, when inserted in vivo. This low efficiency has been pointed out as the result of an underestimated comprehension of the interaction between nanoparticles and biological media, mainly due to the new biological identity of nanoparticles when adsorb biomolecules from physiological fluids. In this context, the aim of this study is the systematic evaluation of the chemical, colloidal and biological properties of multicharged silica nanoparticles (SiO2NPs) obtained from its surface functionalization with zwitterionic groups, bifunctional structures and ionic liquids (IL). These groups have both positive and negative charges and total neutral charge, as well as have shown to be biocompatible and reduce nonspecific adsorption of proteins by structuring the water molecules around them. However, the few papers reported on this matter (or none for IL) have not simultaneously investigated the physicochemical and biological aspects of multicharged nanoparticles, which will regulate the physiological behavior of these nanostructures and their fate in vivo. In this way, multicharged structures will be synthesized and coupled on SiO2NPs surface to understand their effect on colloidal stability and nonspecific adsorption of proteins in physiological media simulated with bivalent ions and in fetal bovine serum. Subsequently, the in vitro behavior of nanostructures will be evaluated by cellular viability assays and hemocompatibility, and the cellular uptake of multicharged nanoparticles will be investigated by microscopy techniques. With this study, it will be possible to create efficient methods of development, evaluation and application of nanoparticles for nanomedicine.
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