No abstract

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.

Despite increasing reports of using silica nanoparticles (SNPs) for controlled drug delivery applications, their long-term toxicity profile following intravenous administration remains unexplored. Herein, we investigated the acute (10-day) and subchronic (60-day and 180-day) toxicity of nonporous SNPs of approximately 50 nm (Stöber SNPs50) and approximately 500 nm in diameter (Stöber SNPs500), and mesoporous SNPs of approximately 500 nm in diameter (MSNPs500) upon single-dose intravenous injection into male and female immune-competent inbred BALB/C mice. The Maximum Tolerated Dose (MTD) of the particles was determined 10 days post-injection. The MTD of SNPs was administered and toxicity evaluated over 60 and 180 days. Results demonstrate that Stöber SNPs50 exhibit systemic toxicity with MTD of 103 ± 11 mg.kg −1 for female and 100 ± 6 mg.kg −1 for male mice, respectively. Toxicity was alleviated by increasing the size of the particles (Stöber SNPs500). MTD values of 303 ± 4 mg.kg −1 for female and 300 ± 13 mg.kg −1 for male were observed for Stöber SNPs500. Mesoporous SNPs500 showed considerable systemic sex-related toxicity, with MTDs ranging from 40 ± 2 mg.kg −1 to 95 ± 2 mg.kg −1 for male and female mice, respectively. Studies of SNPs showed blood toxicity as a function of physiochemical properties such as significant differences in the mean corpuscular hemoglobin (MCHC) and platelet number at day 10 and white blood cell count at day 60. Histological examination also showed size-, porosity-and time-dependent tissue toxicity. Stöber

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.

PSS to our composition can increase the cell viability more than 4 times compared to a nonconductive composition.