Nanocàpsules multimodals de plga per a tècniques d'imatge mèdica i administració de proteïnes i el seu ús potencial en la neuroreparació de lesions isquèmiques cerebrals

Résumé

Advancements in nanoparticulated systems capable of providing the necessary functionalities to new nanomedicines and offering the possibility to combine non-invasive disease detection with individualized treatments are facilitating personalized medicine to become a reality. Besides, the progress in theranostics is shaping the development of image-guided drug delivery improving the efficiency of pharmaceuticals by visualizing their biodistributions, effects on specific molecular and cellular targets, and the corresponding therapeutic effects. This thesis is devoted to engineering theranostic magnetic nano-biomaterials to address neurorepair in the context of an ischemic stroke by enhancing local angiogenesis. Growth factors secreted by endothelial progenitor cells (EPCs-secretome), with proved potential to induce angiogenesis, were encapsulated into magnetic poly(D,L lactic co glycolic acid) (PLGA) nanocapsules. Additionally, this PLGA-drug delivery system was functionalized with versatile imaging reporters allowing magnetic retention and in vitro/in vivo product tracking. The main accomplished objectives of the thesis are: 1) optimization of PLGA nanocapsules for magnetically targeted delivery and controlled encapsulation and release of proteins, 2) modular functionalization of PLGA nanocapsules with versatile imaging reporters: magnetic resonance imaging, fluorescence at four different wavelengths and positron emission tomography and 3) improved approaches to enhance mice brain accumulation of the nanocapsules and to increase EPCs-secretome loading.