Nanoporous silica nanoparticles as biomaterials: evaluation of different strategies for the functionalization with polysialic acid by step-by-step cytocompatibility testing

Abstract

Nanoporous silica materials have become a prominent novel class of biomaterials which are typically applied as nanoparticles or thin films. Their large surface area combined with the rich surface chemistry of amorphous silica affords the possibility to equip this material with variable functionalities, also with several different ones on the same particle or coating. Although many studies have shown that nanoporous silica is apparently non-toxic and basically biocompatible, any surface modification may change the surface properties considerably and, therefore, the modified materials should be checked for their biocompatibility at every step. Here we report on different silane-based functionalization strategies, firstly a conventional succinic anhydride-based linker system and, secondly, copper-catalyzed click chemistry, to bind polysialic acid, a polysaccharide important in neurogenesis, onto nanoporous silica nanoparticles (NPSNPs) of MCM-41 type. At each of the different modification steps, the materials are characterized by cell culture experiments. The results show that polysialic acid can be immobilized on the surface of NPSNPs by using different strategies. The cell culture experiments show that the kind of surface immobilization has a strong influence on the toxicity of the material versus the cells. Whereas most modifications appear inoffensive, NPSNPs modified by click reactions are toxic, probably due to residues of the Cu catalyst used in these reactions.

Mesoporous silica nanoparticles functionalized with hyaluronic acid. Effect of the biopolymer chain length on cell internalization

“…Moreover, the possibility to introduce smart functional groups at the internal and/or the external mesoporous silica surface [9, [26][27][28] allows to promote different types of specific interactions with biological entities. Focusing on mesoporous silica nanoparticles (MSNs), huge improvements were obtained on specific actions such as the MSNs' performance towards the sustained drug release [9, [26][27][28], the reduction of toxicity, the increase of the biocompatibility [10, 29,30] and cell internalization [31], as well as the citotoxicity towards tumor cells [32,33]. Indeed, several target molecules [10, 17,30,[34][35][36][37] and stimuli-responsive capping agents [27,34,[38][39][40][41] can easily be grafted at the MSNs' surface.…”

pH-responsive release of chlorhexidine from modified nanoporous silica nanoparticles for dental applications

“…These cytotoxic molecules are completely removable by calcination at high temperatures. Although, due to their high versatility and diversity, the toxicity assessment of NPSNPs still needs further investigation [40][41][42][43], NPSNPs are generally considered as safe in vitro and in vivo. The US Food and Drug Administration (FDA) recently has approved modified silica nanoparticles for clinical applications [44].…”

Nanotechnology and sialic acid biology

“…PSA can be immobilized on nanoporous silica materials silica nanoparticles (NPSNPs) of MCM-41 type [104] with different applications.…”