Micelas sensibles a pH basadas en polipeptidos sintéticos para aplicaciones en biomedicina

Abstract

Máster en Materiales Nanoestructurados para Aplicaciones Nanotecnológicas (Nanostructured Materials for Nanotechnology Applications).During the past few decades, nanotherapy has proposed a plethora of drug carriers to address serious illnesses such us cancer. These vehicles are, normally, decorated with biomolecules with the aim of delivering their cargo to specific places in the organisms, such as tumoural microenvironments. Nevertheless, when a nanoparticle is introduced into a biological media, it gets covered by a layer of biomolecules, the so-called protein corona. This organic coating diminishes the circulation time and facilitates its excretion. Therefore, an alternative nanoparticle design should be proposed to reduce such recognition. Herein, what is proposed is that a sudden change on the outer shell of the particle would disrupt the protein adhesion, improving both cellular uptake and circulation times. Among all these possible strategies, the slightly lower pH, in the cancer tissue, could be used to provoke such transformation and therefore reduce the protein adhesion. In this project, two different micellar systems, based on synthetic block copolypeptides, were prepared to face off such disruption. The first one is based on poly (glutamic acid) as hydrophilic block, whose conformational change, under acidic pH, would make the micelle instable, avoiding the protein coating. While the other one, based on poly (DMMA-lysine), would rapidly change their surface charge from negative to positive due to a chemical deprotection, and therefore the protein interaction would be interrupted. Block copolypeptides were synthesised monodisperse and in high yields. In addition, the subsequent prepared micellar formulations were successfully isolated and in a very feasible way. Interestingly, different aggregates could be selectively prepared in a controlled and reproducible way, depending on the polymer structure and the fabrication method. The aggregates were found to be pH responsive based on DLS, -potential and circular dichroism studies.Peer reviewe