Mesoporous Silica Nanoparticles: Selective Surface Functionalization for Optimal Relaxometric and Drug Loading Performances

Abstract

Mesoporous silica nanoparticles (MSNs) have emerged as promising biomaterials for drug delivery and cell tracking applications, for which MRI is the medical imaging modality of choice. In this contribution, MRI contrast agents (DTPA‐Gd) and polyethylene glycol (PEG) are grafted selectively at the surface of MSNs, in order to achieve optimal relaxometric and drug loading performances. In fact, DTPA and PEG grafting procedures reported until now, have resulted in significant pore obstruction, which is detrimental to the drug delivery function of MSNs. This usually induces a dramatic decrease in surface area and pore volume, thus limiting drug loading capacity. Therefore, these molecules must be selectively grafted at the outer surface of MSNs. In this study, 3D pore network MSNs (MCM‐48‐type) are synthesized and functionalized with a straightforward and efficient grafting procedure in which DTPA and PEG are selectively grafted at the outer surface of MSNs. No pore blocking is observed, and more than 90% of surface area, pore volume and pore diameter are retained. The thus‐treated particles are colloidally stable in SBF and cell culture media, they are not cytotoxic and they have high drug loading capacity. Upon labeling with Gd, the nanoparticle suspensions have strong relaxometric properties (r2/r1 = 1.47, r1 = 23.97 mM−1 s−1), which confers a remarkable positive contrast enhancement potential to the compound. The particles could serve as efficient drug carriers, as demonstrated with a model of daunorubicin submitted to physiological conditions. The selective nanoparticle surface grafting procedures described in the present article represent a significant advance in the design of high colloidal stability silica‐based vectors with high drug loading capacity, which could provide novel theranostic nanocompounds.

Relaxivity Enhancement of Ditopic Bishydrated Gadolinium(III) Complexes Conjugated to Mesoporous Silica Nanoparticles

“…An important finding was the observation of enhanced relaxivity for Gd III chelates selectively linked to the external surface of the MSNs, and this behaviour was associated with limited water diffusion inside the pores, as this prevents the efficient transfer of the paramagnetic effect to the bulk water. Furthermore, other relevant studies on Gd‐based MSNs for MRI or theranostic applications have been reported in recent years . It should be emphasized that the great majority of the considered complexes are represented by functionalized GdDTPA or GdDTPA‐monoamide chelates.…”

“…(A) Schematic view of the synthetic pathway for Gd 2 L 2 ‐MSN‐PEG and the structure of Gd 2 L 1 . (B) HRTEM micrographs of the MSN sample at low and high magnifications.…”

Cancer‐Cell‐Specific Nuclear‐Targeted Drug Delivery by Dual‐Ligand‐Modified Mesoporous Silica Nanoparticles

“…Nevertheless, the loading capability of FA-MSN-DEX is still higher than that of several recently reported silicabased delivery systems [ 41,42 ] and an optimal balance between effective targeting and high drug loading may be achieved by further tuning the quantity of the functional groups. [ 43 ] In vitro release tests show that the three kinds of MSNs display similarly sustained and pH-dependent release profi les with faster drug release at pH 5.0 than at pH 7.4, which could be attributed to the increased solubility of DOX at lower pH ( Figure S12, Supporting Information). [ 44 ] Besides, the surface-modifi ed samples show lower DOX release rate compared to pMSN, which suggests the functional groups on the external surface may also affect the outward diffusion of DOX.…”

Gold Nanorattles with Intense Raman In Silica Nanoparticles (Nano‐IRIS) as Multimodal System for Imaging and Therapy

“…Results clearly showed a pH dependent release of DOX (Figure S3b) from the Nano‐IRIS over time. In acidic conditions, the SiO − groups present in silica framework gets protonated and induce the release of DOX from the silica surface, whereas at normal pH (pH=7.4) the silica surface predominantly stays as SiO − which strongly interacts with the DOX and keep it intact on the surface, thereby minimizing its release …”