Surface Modification of Silica Nanoparticles to Reduce Aggregation and Nonspecific Binding

Abstract

In this paper, a systematic study of the design and development of surface modification schemes for silica nanoparticles is presented. The nanoparticle surface design involves an optimum balance of the use of inert and active surface functional groups to achieve minimal nanoparticle aggregation and reduce nanoparticle non-specific binding. Silica nanoparticles were prepared in a water-in-oil microemulsion and subsequently surface modified via co-hydrolysis with tetraethylorthosilicate (TEOS) and various organosilane reagents. Nanoparticles with different functional groups, including carboxylate, amine, amine/phosphonate, polyethylene glycol, octadecyl, and carboxylate/octadecyl groups were produced. Aggregation studies, using SEM, dynamic light scattering, and zeta potential analysis, indicate that severe aggregation among amine-modified silica nanoparticles can be reduced by adding inert functional groups, such as methyl phosphonate, to the surface. To determine the effect of various surface modification schemes on nanoparticle non-specific binding, the interaction between functionalized silica nanoparticles and a DNA chip was also studied using confocal imaging/ fluorescence microscopy. Dye-doped silica nanoparticles functionalized with octadecyl and carboxylate groups showed minimal non-specific binding. Using these surface modification schemes, fluorescent dye-doped silica nanoparticles can be more readily conjugated with biomolecules and used as highly fluorescent, sensitive, and reproducible labels in bioanalytical applications.

Assessing nanoparticle toxicity in cell-based assays: influence of cell culture parameters and optimized models for bridging the in vitro–in vivo gap

“…Therefore some groups have focussed on the development of methods to create a stable and uniform dispersion via surface modification, addition of surfactants etc. [118][119][120] . But opposing opinions exist on whether NP agglomerates must be redispersed before addition to the cells or not since results from a study by Oberdörster et al in which surfactant stabilised dispersions were used, has been put to question as the observed toxicity might have been caused by surfactant residuals 121 .…”

A comparison of mono and multivalent linkers and their effect on the colloidal stability of nanoparticle and immunoassays performance

“…Dye-doped silica nanoparticles [13][14][15] (NP) stand out as excellent candidates as it is possible to dope silica NPs with a large number of fluorophores, increasing the total fluorescence of the label significantly [16,17]. Moreover, the fluorophore is protected inside a silica matrix, thereby increasing photostability [18,19] and quantum efficiency [20,21].…”

“…Silica NPs are also relatively non-toxic, chemically inert, and can be prepared in a range of sizes [22]. It also relatively easy to functionalize silica NP with bioreactive groups that enable facile bioconjugation [16,22,23].…”

“…We believe this is a significant stumbling block in the development of silica NP labels. In 2006, Tan and colleagues [16] proposed a way of improving colloidal stability of silica NPs through the addition of a negatively charged non-reactive organosilane alongside the bioreactive organosilane. In this paper we extend this work and show the significance, both for colloid stability and for assay performance, of the choice of the bi-linker, used to conjugate the detection antibody to the functionalised NP.…”

“…While a lot of work has been published on the functionalization of silica NP with a reactive organosilane [16,26], to our best knowledge, no systematic studies have been reported for the optimization of the linker chemistry. There is a great choice of commercial hetero-or homo-functional linkers available; however, their effect on NP stability, aggregation, solubility and efficiency of bioconjugation is poorly documented.…”