Formulación de nanopartículas biocompatibles y multifuncionales contra el cáncer

Résumé

Cancer is a heterogenous and dynamic disease that requires a more personalized medicine. Nanotechnology goals is to give an answer to this necessity by means of the engineering of controlled drug delivery systems to enhance both efficacy and safety chemotherapy profile but also to develop novel therapeutic approaches and advanced diagnostic tools. Current research efforts aim to design multifunctional platforms for an improved cancer prognosis. In that sense, iron oxides are one of the most promising nanomaterials. The PhD thesis main purpose is to design a biocompatible nanosystem for combined antitumoral treatment based on chemotherapy and magnetic hyperthermia and diagnosis capability via magnetic resonance imaging. With that aim, a reproducible obtaining methodology has been developed for magnetic nanoparticles inclusion into a poly(ε-caprolactone) matrix which was then functionalized using chitosan. Resultant nanocomposites have been submitted to an extensively characterization for size, structure, chemical composition, electrical charge and thermodynamic surface, colloidal stability and magnetic capability. Nanoplatform biocompatibility has been researched using proliferation and morphologic cellular assays whereas parenteral administration has been validated through an haemocompatibility evaluation. Control gemcitabine delivery nanocomposites potential has been investigated by exhaustive in vitro tests of drug payload and release in addition to the induced cytotoxicity in tumour cells. Antitumoural magnetic hyperthermia nanosystems possibilities have been explored by applying electromagnetic fields to tumoral cell lines cultures. Magnetic relaxitivity was also studied for nanoparticle validation as a contrast agent in magnetic resonance imaging. Taking into account nanoparticle capacity as a T2 contrast agent, biodistribution experiments have been realized. In view of the results obtained, it can be concluded that magnetite/poly(ε- caprolactone)]/chitosan nanoparticles constitute a biocompatible multifunctional tool (chemotherapy + hyperthermia + contrast agent for magnetic resonance imaging) with promising possibilities for the theragnosis against cancer.