A Toolbox for the Synthesis of Multifunctionalized Mesoporous Silica Nanoparticles for Biomedical Applications.

Cornelia Von Baeckmann,Hanspeter Kählig,Damien Renfer,Rémy Guillet-Nicolas,Freddy Kleitz

doi:10.1021/acsomega.8b02784

Cornelia Von Baeckmann, Hanspeter Kählig + Show 3 more

Open Access

https://doi.org/10.1021/acsomega.8b02784

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Journal: ACS omega	Publication Date: Dec 17, 2018
Citations: 49	License type: cc-by

Affiliation: University of Vienna, Université Laval

Abstract

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 stability of the different systems was evaluated in physiological media, and preliminary tests were performed to verify their drug release capability. The use of MPTS appeared beneficial when compared to APTS in delayed co-condensation procedures to preserve both selective distribution of 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 by the sequence of step-by-step functionalization methods aiming to produce multipurpose and stable bioplatforms.

Highlights

Mesoporous silica nanoparticles (MSNs) are promising candidates for biomedicine-related applications,[1−10] and they are used in the area of targeted and controlled drug delivery,[11−16] as well as in medical imaging/diagnosis[17−20] or in a combination of both, that is, theranostic systems.[21−25] The growing interest for MSNs is directly related to their porosity features
Larger nonlocal density functional theory (NLDFT) pore size and total pore volume were obtained for the extracted material (3.5 nm and 1.0 cm[3] g−1) as compared to the calcined one (3.2 nm and 0.8 cm[3] g−1) in accordance with the shrinkage occurring during the calcination process.[71]
We demonstrated the importance of the different MSN synthesis and functionalization methods and steps in order to produce the most efficient platform for biorelated applications while preserving the integrity and the features of the mesopore structure

Summary

Introduction

Mesoporous silica nanoparticles (MSNs) are promising candidates for biomedicine-related applications,[1−10] and they are used in the area of targeted and controlled drug delivery,[11−16] as well as in medical imaging/diagnosis[17−20] or in a combination of both, that is, theranostic systems.[21−25] The growing interest for MSNs is directly related to their porosity features These materials are highly porous, with a specific surface area of about 1000−1500 m2 g−1, mesopores of size usually ranging from 2 to 20 nm and pore volume ranging from 0.8 to 1.5 cm[3] g−1.26−28 In addition, MSNs are seen as versatile materials because they can be synthesized with welldefined particle size and shape as well as tunable pore network characteristics.[29,30] Currently, data regarding the potential adverse effects of MSNs on overall human health on the midterm and long term are still missing, that is, no clinical trials have been performed yet.[31,32] amorphous silica is so far considered safe by the Food and Drug Administration and has been extensively used in many of our daily-based products or as excipient in pharmaceutical formulations for many years.[33] Owing to their porosity, their relative stability in aqueous media, and degradation in biological media, MSNs became of interest as drug reservoir and bioimaging platforms. A large variety of therapeutic compounds can be accommodated inside their pore network, and many examples using such particles as hosts to improve the administration of simple

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