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Slight alterations in nanoparticles’ surface properties can significantly influence the corona composition which may alter their interaction with the biological milieu. Size and porosity of silica nanoparticles (SNPs) are known to be predominant factors influencing their dose-dependent toxicity. Little is known however about the extent and type of protein adsorption on SNPs as a function of physicochemical properties and the role this might play on mechanisms of cellular uptake and toxicity. In this work we investigated the influence of size and porosity of SNPs on protein adsorption, cellular uptake, and toxicity in RAW 264.7 macrophages. Toxicity of the SNPs was found to be concentration dependent, and the formation of the protein corona mitigated toxicity for all particles. Detailed analysis of the amount of proteins recovered from each nanoparticle revealed similarities in the protein adsorption profile as a function of size and porosity. The mechanism of uptake was highly dependent on size rather than porosity or the adsorbed proteins.

Design and development of silica nanoparticles (SiO2 NPs) with a controlled degradation profile promises effective drug delivery with a predetermined carrier elimination profile. In this research, we fabricated a series of redox-responsive polysulfide-based biodegradable SiO2 NPs with low polydispersity and with variations in size (average diameters of 58 ± 7, 108 ± 11, 110 ± 9, 124 ± 9, and 332 ± 6 nm), porosity, and composition (disulfide vs tetrasulfide bonds). The degradation kinetics of the nanoparticles was analyzed in the presence of 8 mM glutathione (GSH), mimicking the intracellular reducing condition. Results indicate that porosity and core composition play the predominant roles in the degradation rate of these nanoparticles. The 108 nm mesoporous disulfide-based nanoparticles showed the highest degradation rate among all the synthesized nanoparticles. Transmission electron microscopy (TEM) reveals that nonporous nanoparticles undergo surface erosion, while porous nanoparticles undergo both surface and bulk erosion under reducing environment. The cytotoxicity of these nanoparticles in RAW 264.7 macrophages was evaluated. Results show that all these nanoparticles with the IC50 values ranging from 233 ± 42 to 705 ± 17 μg mL−1 do not have cytotoxic effect in macrophages at concentrations less than 125 μg mL−1. The degradation products of these nanoparticles collected within 15 days did not show cytotoxicity in the same macrophage cell line after 24 h of incubation. In vitro doxorubicin (DOX) release was examined in 108 nm mesoporous disulfide-based nanoparticles in the absence and presence of 8 mM GSH. It was shown that drug release depends on intracellular reducing conditions. Due to their ease of synthesis and scale up, robust structure, and the ability to control size, composition, release, and elimination, biodegradable SiO2 NPs provide an alternative platform for delivery of bioactive and imaging agents.

The biological activity of the immobilized enzyme is crucial for the performance of different nanoparticle mediated enzymatic assays, where enzymatic conversion can be used for label-free analyte detection. In this article we have addressed two significant aspects of enzyme-nanoparticle interactions. First, we have developed copper sulfide (CuS) nanoparticles with an average diameter of 25 nm as a potential enzyme-interface using trypsin protease as a model enzyme. CuS nanoparticles showed high trypsin immobilization capacity of about 14.0 mg m(-2) with the significant retention of native enzymatic activity (75-98%) at room temperature, even beyond the calculated tightly packed monolayer coverage (which is around 4.1 mg m(-2)). Second, we report a quantitative correlation between the structure-functional relationship and the density of immobilized trypsin on a nanoparticle surface. The in situ conformation of immobilized trypsin could be efficiently analyzed by fluorescence, circular dichroism and FT-IR spectroscopic measurements because of the small size of the nanoparticles. Trypsin molecules appear to retain their close-native tertiary and secondary structural features (with a small loss of 1-2% of helical content) in the entire surface density range (2.0-14.0 mg m(-2)) on the CuS nanoparticles. However, interestingly, at a low surface coverage (2.0 mg m(-2)), immobilized trypsin retains almost 98% of its native enzymatic activity, leading to a highly functional bio-nanocomposite. However, at higher surface coverages, the enzyme activity decreases to 77%, indicating the influence of steric crowding. Furthermore, the high functionality of the immobilized trypsin at low surface density on CuS nanoparticle was also confirmed by determining the kinetic parameters of enzymatic activity.

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Silica nanoparticles are extensively used in biomedical applications and consumer products. Little is known about the interaction of these NPs with the endothelium and effect on platelet adhesion under flow conditions in circulation. In this study, we investigated the effect of silica nanoparticles on the endothelium and its inflammation, and subsequent adhesion of flowing platelets in vitro. Platelet counts adhered onto the surface of endothelial cells in the presence of nanoparticles increased at both low and high concentrations of nanoparticles. Preincubation of endothelial cells with nanoparticles also increased platelet adhesion. Interestingly, platelet adhesion onto TNF-α-treated endothelial cells decreased in the presence of nanoparticles at different concentrations as compared with the absence of nanoparticles. We monitored the expression of different endothelial proteins, known to initiate platelet adhesion, in the presence and absence of silica nanoparticles. We found that silica nanoparticles caused changes in the endothelium such as overexpression of PECAM that promoted platelet adhesion to the endothelial cell.