A Toolbox for the Synthesis of MultifunctionalizedMesoporous Silica Nanoparticles for Biomedical Applications

摘要

Mesoporous silica nanoparticles (MSNs) are considered as promising next-generation nanocarriers for health-related applications. However, their effectiveness mostly relies on their efficient and surface-specific functionalization. In this contribution, we explored different strategies for the rational multistep synthesis of functional MCM-48-type MSNs with selectively created active inner and/or external surfaces. Functional groups were first installed using a combination of (delayed) co-condensation and post-grafting procedures. Both amine [(3-aminopropyl)triethoxysilane (APTS)] and thiol [(3-mercaptopropyl)trimethoxysilane (MPTS)] silanes were used, in various addition sequences. Following this, the different platforms were further functionalized with polyethylene glycol and/or with a pro-chelate ligand used as a magnetic resonance imaging contrast agent (diethylenetriaminepentaacetic acid chelates) and/or loaded with quercetin and/or grafted with an organic dye (rhodamine). The efficiency of the multiple grafting strategies and the effects on the MSN carrier properties are presented. Finally, the colloidal stabilityof the different systems was evaluated in physiological media, andpreliminary tests were performed to verify their drug release capability.The use of MPTS appeared beneficial when compared to APTS in delayedco-condensation procedures to preserve both selective distributionof the functional groups, reactive functionality, and pore ordering.Our results provide in-depth insights into the efficient design of(multi)functional MSNs and especially on the crucial role played bythe sequence of step-by-step functionalization methods aiming to producemultipurpose and stable bioplatforms.