Cytotoxicity of mesoporous silica nanomaterials

Pasqua, Anthony J. Di; Sharma, Krishna K.; Yan, Shuang; Toms, Bonnie B.; Ouellette, Wayne; Dabrowiak, James C.; Asefa, Tewodros

doi:10.1016/j.jinorgbio.2007.12.028

Cited by 213 publications

(158 citation statements)

References 36 publications

(51 reference statements)

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“…MCM-41 has been shown to exert concentration dependent toxicity on human T cell lymphoma and adenocarcinoma cells, but was not shown to elicit any toxicity or cell differentiation in mesenchymal stem cells. [8][9][10] Nevertheless, some of the data on MCM-41 cell-based screens were found to be misleading due to the interference of MCM-41 itself with the 2,5-diphenyltetrazolium salt (MTT) used to asses toxicity. 11,12 Iron oxide NPs (Fe 2 O 3 or Fe 3 O 4 ) have been widely applied as magnetic drug targeting systems 13,14 and contrast agents in magnetic imaging.…”

Section: 7mentioning

confidence: 99%

Evaluation of Toxicity and Gene Expression Changes Triggered by Oxide Nanoparticles

Dua¹,

Chaudhari²,

Lee³

et al. 2011

Bulletin of the Korean Chemical Society

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Several studies have demonstrated that nanoparticles (NPs) have toxic effects on cultured cell lines, yet there are no clear data describing the overall molecular changes induced by NPs currently in use for human applications. In this study, the in vitro cytotoxicity of three oxide NPs of around 100 nm size, namely, mesoporous silica (MCM-41), iron oxide (Fe 2 O 3 -NPs), and zinc oxide (ZnO-NPs), was evaluated in the human embryonic kidney cell line HEK293. Cell viability assays demonstrated that 100 µg/mL MCM-41, 100 µg/mL Fe 2 O 3 , and 12.5 µg/mL ZnO exhibited 20% reductions in HEK293 cell viability in 24 hrs. DNA microarray analysis was performed on cells treated with these oxide NPs and further validated by real time PCR to understand cytotoxic changes occurring at the molecular level. Microarray analysis of NP-treated cells identified a number of up-and down-regulated genes that were found to be associated with inflammation, stress, and the cell death and defense response. At both the cellular and molecular levels, the toxicity was observed in the following order: ZnO-NPs > Fe 2 O 3 -NPs > MCM-41. In conclusion, our study provides important information regarding the toxicity of these three commonly used oxide NPs, which should be useful in future biomedical applications of these nanoparticles.Key Words : MCM-41, Fe 2 O 3 nanoparticle, ZnO nanoparticle, HEK293, Microarray Introduction Nanoparticles (NPs) have increased surface area to weight ratios relative to the same materials in the non-nano size range. In addition to unusual physical properties, NPs are also more chemically reactive than larger particles, which can be either advantageous or harmful depending on their end use. The nanotech boom started around a decade ago and since then the use of NPs in consumer goods and biomedical applications has dramatically increased. NPs are increasingly applied as drug delivery vehicles, biosensors, imaging contrast reagents, and therapeutic agents. However, it is surprising that even today the scientific and industrial community has no sufficiently clear data on the overall effects of these NPs on human health.NPs are easily internalized into cells 1,2 and some NPs have even been shown to cross the blood brain barrier 3-5 where they alter biological processes and cause toxicity. Various in vitro and in vivo studies indicate that some NPs are associated with serious toxicity issues. The most commonly used in vitro toxicity tests focus on whether potentially toxic agents result in cell death. However, sublethal cellular changes may also exist that are not visible in such toxicity screens, but may significantly affect biological processes at the organismal level. Hence, it is important to identify overall cellular changes mediated by NP exposure. Identification of molecular signatures of toxicity at the genomic or proteomic levels provides comprehensive and reliable high throughput data. These data can then be used to compare, classify, and grade a NP on a scale of toxicity. In the present study we identified the m...

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Section: 7mentioning

confidence: 99%

Evaluation of Toxicity and Gene Expression Changes Triggered by Oxide Nanoparticles

Dua¹,

Chaudhari²,

Lee³

et al. 2011

Bulletin of the Korean Chemical Society

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“…lee et al acute and repeat dose toxicities, and biokinetics, [11][12][13][14][15][16][17][18][19] which are currently hot issues in the nanotoxicology field. However, the kinetic behaviors of silica nanoparticles at the systemic level, including their pharmacokinetics, tissue distributions, and clearances, remain unclear.…”

mentioning

confidence: 99%

Tissue distribution and excretion kinetics of orally administered silica nanoparticles in rats

An¹,

Lee²,

Kim³

et al. 2014

IJN

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Purpose The effects of particle size on the tissue distribution and excretion kinetics of silica nanoparticles and their biological fates were investigated following a single oral administration to male and female rats. Methods Silica nanoparticles of two different sizes (20 nm and 100 nm) were orally administered to male and female rats, respectively. Tissue distribution kinetics, excretion profiles, and fates in tissues were analyzed using elemental analysis and transmission electron microscopy. Results The differently sized silica nanoparticles mainly distributed to kidneys and liver for 3 days post-administration and, to some extent, to lungs and spleen for 2 days post-administration, regardless of particle size or sex. Transmission electron microscopy and energy dispersive spectroscopy studies in tissues demonstrated almost intact particles in liver, but partially decomposed particles with an irregular morphology were found in kidneys, especially in rats that had been administered 20 nm nanoparticles. Size-dependent excretion kinetics were apparent and the smaller 20 nm particles were found to be more rapidly eliminated than the larger 100 nm particles. Elimination profiles showed 7%–8% of silica nanoparticles were excreted via urine, but most nanoparticles were excreted via feces, regardless of particle size or sex. Conclusion The kidneys, liver, lungs, and spleen were found to be the target organs of orally-administered silica nanoparticles in rats, and this organ distribution was not affected by particle size or animal sex. In vivo, silica nanoparticles were found to retain their particulate form, although more decomposition was observed in kidneys, especially for 20 nm particles. Urinary and fecal excretion pathways were determined to play roles in the elimination of silica nanoparticles, but 20 nm particles were secreted more rapidly, presumably because they are more easily decomposed. These findings will be of interest to those seeking to predict potential toxicological effects of silica nanoparticles on target organs.

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“…This might be attributed to the bare surface of the MMSNs used in our experiments, which could be eliminated by surface modification in further application. 53 In contrast, both individual and combinative loading groups produced dose-dependent tumor cell growth inhibitions. Particularly, the inhibition effect of the multidrug-loaded MMSNs was more significant than that of single-drug-loaded MMSNs.…”

Section: Improved Cancer Cell Killing and Inhibition By The Multidrugmentioning

confidence: 99%

Delivering hydrophilic and hydrophobic chemotherapeutics simultaneously by magnetic mesoporous silica nanoparticles to inhibit cancer cells

Liu¹,

Zhang²,

Sun³

et al. 2012

IJN

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Using nanoparticles to deliver chemotherapeutics offers new opportunities for cancer therapy, but challenges still remain when they are used for the delivery of multiple drugs, especially for the synchronous delivery of hydrophilic and hydrophobic drugs in combination therapies. In this paper, we developed an approach to deliver hydrophilic-hydrophobic anticancer drug pairs by employing magnetic mesoporous silica nanoparticles (MMSNs). We prepared 50 nm-sized MMSNs with uniform pore size and evaluated their capability for the loading of two combinations of chemotherapeutics, namely doxorubicin-paclitaxel and doxorubicinrapamycin, by means of sequential adsorption from the aqueous solution of doxorubicin and nonaqueous solutions of paclitaxel or rapamycin. Experimental results showed that the present strategy successfully realized the co-loading of hydrophilic and hydrophobic drugs with high-loading content and widely tunable ratio range. We elaborate on the theory behind the molecular interaction between the silica hydroxyl groups and drug molecules, which underlie the controllable loading, and the subsequent release of the drug pairs. Then we demonstrate that the multidrug-loaded MMSNs could be easily internalized by A549 human pulmonary adenocarcinoma cells, and produce enhanced tumor cell apoptosis and growth inhibition as compared to single-drug loaded MMSNs. Our study thus realized simultaneous and dose-tunable delivery of hydrophilic and hydrophobic drugs, which were endowed with improved anticancer efficacy. This strategy could be readily extended to other chemotherapeutic combinations and might have clinically translatable significance.

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Cytotoxicity of mesoporous silica nanomaterials

Cited by 213 publications

References 36 publications

Evaluation of Toxicity and Gene Expression Changes Triggered by Oxide Nanoparticles

Evaluation of Toxicity and Gene Expression Changes Triggered by Oxide Nanoparticles

Tissue distribution and excretion kinetics of orally administered silica nanoparticles in rats

Delivering hydrophilic and hydrophobic chemotherapeutics simultaneously by magnetic mesoporous silica nanoparticles to inhibit cancer cells

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