Controlled protein delivery from thermo-responsive nanoparticles and composite scaffolds for nanomedicine and tissue engineering applications

Overview & Synopsis

The use of proteins as therapeutic agents has been studied since decades due to their multiple advantages such as their specificity and their wide range of applications. However, their fragility and their short half-life in the blood stream, coupled with their poor membrane permeability, make their use tricky. The objective of this PhD was to study the use of stellate mesoporous silica nanoparticles (STMS NPs) and core-shell iron oxide @ STMS (IO@STMS) NPs as building blocks to develop smart protein delivery systems by combining them with thermo-responsive materials. We could show that the functionalization of STMS with the isobutyramide (IBAM) group, a molecular glue, allowed the sustained release of active proteins in conditions mimicking the dynamic blood flow. We also studied the STMS functionalization with thermo-responsive polymers, either by grafting on STMS or by adsorption on STMS@IBAM. We could notably show that the adsorption of hydroxypropyl-cellulose or Pluronic F127 brought an anti-fouling property to the particles. The STMS have also been integrated in a model hydrogel and we could obtain a control of the protein retention inside the hydrogel by controlling the quantity of STMS, acting as protein reservoirs. Finally, we studied in details the growth of the silica shell on the iron oxide core and the impact of the shell thickness on the MRI and magneto- and photo-thermal properties of the core.