6533b7d0fe1ef96bd125b417

RESEARCH PRODUCT

Synthesis of mesoporous silica nanoparticles (MSNs) and encapsulation of cisplatin for targeted cancer therapies

subject

description

The aim of this PhD thesis is to elaborate mesoporous silica nanoparticles (MSNs) able to sustain the release of cisplatin into the intracellular compartments of solid tumors. The parametric study shows that morphological, structural and textural properties of MSNs-MCM-41, synthesized by sol-gel reaction by using TEOS as a silica source and CTAB as a structure-directing agent, depend on pH, stirring speed, temperature and extraction process of CTAB. The synthesis atmosphere has to be controlled in order to avoid the presence of ethanol and carbonate species which are responsible of necks between particles generating unstable suspensions of MSNs.MSNs were functionalized in order to control the interactions between cisplatin and MSNs or to improve their colloidal stability in physiological media.Various silanated organic molecules (APTES, TESP, MPTES, CEST) and neutral or ionised polymers were grafted into the MSNs using a co-condensation approach or a postsynthetic functionalization method while keeping structural and textural properties of MSNs unchanged.The amount of cisplatin encapsulated by using impregnation are higher than those obtained by using adsorption and depend on MSNs fonctionalization. MSNs grafted by PEI allow a sustained drug release and cytotoxic effects similar to cisplatin. In vitro assays show that MSNs devoid of cisplatin are not cytotoxic up to 200 µg/mL. Confocal microscopy study reveals that MSNs internalization is efficient after about 2h of contact with cells.