Healthcare applications of Stimuli-Responsive Elastin-Like Polypeptide Nanocarriers

Descripción del proyecto

Aplicaciones sanitarias de coacervados de polipéptidos similares a la elastina como vehículos de administración de fármacos

Una administración de fármacos eficiente requiere unos transportadores que respondan a estímulos con la posibilidad de desencadenar la liberación de los fármacos al alcanzar el tejido diana. Los polipéptidos similares a la elastina (ELP, por sus siglas en inglés) son biopolímeros modificados genéticamente que presentan un comportamiento de transición de fase a una temperatura de solución crítica más baja definida. Son solubles por debajo de su temperatura de transición y se agrupan en coacervados por encima de dicha temperatura. Esta transición también es reversible. El proyecto financiado con fondos europeos HsrELPnano pretende estudiar un conjunto de ELP dependiente de la velocidad de calentamiento recientemente descubierto y aplicarlo a la administración de fármacos. El objetivo es diseñar nanotransportadores novedosos de ELP que puedan administrar un tratamiento efectivo «in vivo» ante factores desencadenantes como el pH, los entornos de reducción-oxidación o la hipertermia magnética.

Objetivo

One of the main challenges in drug delivery is the fabrication of carriers that possess a molecular trigger or property that induces tumor cell death or activates the release of the drug cargo from the vehicle once it has reached the desired place of action. Elastin like polypeptides (ELPs) are genetically engineered protein polymers with a reversible ability to from nanoparticles by phase separation when they are above its transition temperature (Tt), while below Tt they remain solubilized. My proposal aims to study a cutting-edge finding about a recently discovered thermal pathway-dependent assembly of ELPs and translate it into innovative solutions in drug delivery. This unique feature allows protein payloads to partake in the co-assembly itself making possible to encapsulate and protect the macromolecular cargoes in the nanoparticle interior. Additionally, I will expand this encapsulation possibilities to magnetic nanoparticles. HsrELPnano will enlarge the scope of the pathway-dependent co-assembly of ELPs. A further understanding and control of these assembly mechanisms will contribute to expanding the toolbox of stimuli-responsive systems, especially to their application as drug delivery systems. The final goal is to design novel ELP nanocarriers that can deliver a treatment in vivo under specific stimuli as pH, redox environment by therapeutic agents and magnetic hyperthermia. To carry out this project, ELPs will be engineered to assemble into nanoparticles above physiological temperature followed by internal crosslinking to retain their structure also below the Tt. Since the crosslinkers can be designed to render this susceptibility to specific triggers the coacervates will disassemble under these stimuli, releasing their payload within the target tissue. This action will enhance my future career prospects and skills, fulfilling an end-to-end training from synthesis to application, which is highly appealing in this multidisciplinary field.