Glycan-coated nanoparticles for the enhanced active targeting

Resumen

Gold nanoparticles (AuNPs) are nanomaterials with excellent physicochemical and optical properties for a broad range of applications. The surface functionalization of the AuNPs enables the formation of glyco-gold nanoparticles (GAuNPs). GAuNPs multivalency properties can trigger the cluster glycoside effect overcoming the low affinity between individual carbohydrate-protein interactions. Therefore, these nanoparticles (NPs) have been demonstrated to be excellent candidates for lectin targeting among other biological applications.Moreover, AuNPs when in contact with biological media interact with the present proteins forming the protein corona (PC) which has an effect in the final fate and efficacy of the NPs. The study of the PC formation of the NPs is extremely important to assure the activity of the AuNPs. The PC formation can be modulated with the surface coating, size, and shape of the AuNPs. Ligand stabilizers as for example polyethylene glycol (PEG) can prevent the PC formation and the consequent recognition by the immune system and clearance of the body. Additionally, the glycan coating of the AuNPs can also modulate the PC composition and therefore the biodistribution of the GAuNPs can be modified.The final aim of this project is the increase of the circulation time of glyco-nanomaterials in the body in order to enhance the active targeting. To accomplish this objective some features of the nanomaterials such as size, shape, surface coating, and composition were considered as they play a crucial role. The modulation of these features can highly impact the protein corona formation when in contact with biological media and consequently the half-life of the nanomaterials. The size was tuned by designing a new synthetic procedure for the synthesis of glyco ultra-small gold nanoparticles. The effect over the half-life of the nanoparticles of AuNPs with different surface coating was studied by performing biodistribution studies in healthy mice and novel Glyco-PEGylated polyamine phosphate nanoparticles were synthesized.The results obtained throughout this thesis contribute to the advance of the research of glyco nanomaterials towards the production of new nanomedicines. As it provides a better understanding of crucial aspects regarding their future applications. Moreover, a novel synthetic procedure of ultra-small GAuNPs was developed overcoming some of the current challenges in nanoparticles production as it enables an easy scale-up, it is an automated system, and it offers a fine control over the surface coating of the nanoparticles.