Design considerations for mesoporous silica nanoparticulate systems in facilitating biomedical applications

Abstract

Mesoporous silica nanoparticles (MSNs) have advanced to the forefront of multifunctional nanoparticulate systems in nanomedicine, owing to this highly fexible materials platform enabling a multitude of design options, often in a modular fashion. Drug delivery ability, detectability via diferent imaging modalities, and stimuliresponsiveness are often combined into one particle system. Very sophisticated and versatile designs along with impressive demonstrations of applicability have been reported to date, but a common ground when it comes to some critical considerations valid for any nanoparticle intended for biomedical purposes is lacking to some degree. In this study, we attempt to take a glance at some of the most crucial aspects of biomedical nanoparticulate design and relate how they apply specifically toMSNs. These considerations include fuorophore labeling and leaching with respect to immobilization to MSNs, the surrounding conditions, carrier biodegradability, and surface coating. Surface modifcation strategies and surface charge tuning are further considered in conjunction to the relative amount of cellular uptake and serum protein adsorption. Cellular internalization routes and biological techniques used to evaluate especially in vitro biobehavior are discussed. Our attempt is hereby to draw attention to some of the most frequently occurring issues to be considered in the design of MSN systems for biomedical applications

Targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles

“…A boosting effect of FA on cellular uptake was only, but clearly, detected in the case when FA was linked to PEGylated particles where PEG was conjugated to the MSNs directly, without an intermediate PEI layer; and for which the basal uptake was thus, was low. All particles functionalized with PEI were internalized more efficiently than their counter-particle without PEI, in accordance with our previous studies 22,33 ( Figure S4A and B), and we have previously shown that this type of particles were internalized by the clathrin-mediated endocytosis route. 22 Particles without any polymeric coating or only modified with PEG showed low uptake probably associated with their almost neutral charge as well as tendency to aggregate at neutral conditions (Table 1).…”

“…As the fluorescence intensity of fluorescein varies depending on the surrounding pH 38 as well as the particle functionalization regime 22,32 (Table 1), we detected the percent of cells which have internalized particles as a measure of uptake efficiency (Figure 2A). In Caco-2 cells, the cellular uptake was determined as a function of cell confluency.…”

“…MSNs were synthesized as previously described adopting a co-condensation approach 22,32,33 further modified by functionalization for cellular and oral delivery with PEI, PEG, and FA as described in the "Experimental" section, and summarized in Figure 1. The resulting particles and their physicochemical characteristics are summarized in Table 1.…”

“…Briefly, MSNs were synthesized according to previously published protocols. 22,32,33 Surfactant-extracted MSNs were functionalized with PEI by surface hyperbranching polymerization of PEI as previously reported to yield PEI-MSNs. 34 Both plain MSNs and PEI-MSNs were further functionalized with PEG utilizing the primary amine groups of either the aminosilane (for plain MSNs) or terminal ends of PEI (for PEI-MSNs).…”

“…Pure PEI has been shown to result in toxic side effects directly related to the molecular weight of branched PEI, which would restrict its application for therapeutic drug delivery. 19 However, derivatization or "charge capping" of PEI with other functional groups 20,21 as well as when used as a constituent together with silica in the construction of hybrid materials 22 has indicated that these drawbacks of pure PEI can be restrained. Poly(ethylene glycol) (PEG) is the most commonly used nonionic hydrophilic polymer in biomedical drug delivery design because it has been shown to reduce uptake by the reticuloendothelial system, provide good dispersibility in aqueous solvents, and diminish association with proteins.…”