Clinical translation of silica nanoparticles.
Ontology highlight
ABSTRACT:
SUBMITTER: Janjua TI
PROVIDER: S-EPMC8496429 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Expansion of nanotechnology will bring many potential benefits as adversely effects on human health. Protection of the human respiratory system from exposure of volatile nanoparticles has become an emerging health concern. The understanding of the biological processes involved in the development and maintenance of a variety of pathologies is improved by genome-wide approaches. Technical feasibility of this type of experiment has perfected in recent years, but data analysis remains challenging. In this context, gene set analysis has emerged as a fundamental tool for the interpretation of the results. We demonstrate how the use of a combination of gene-by-gene and gene set analyses can enhance the interpretation of results. Gene set analyses are able to distinguish responses due to nanoparticle size also discriminating between long and short time recovery after exposure. Transcription regulation and cell proliferation modulation appear to be an early response while oxidative stress and mitochondrial perturbation are late response. Moreover, smaller the particle higher the effect on inflammatory response and DNA damage activation. By integrating the two approaches, we evidenced the importance of MMP1, MMP9, MMP7 and MMP14 genes in response to Ludox® silica nanoparticles and the involvement apoptosis process in cell viability.
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Project description:BackgroundMesoporous silica (MPS) nanoparticles (NPs), which have a unique pore structure and extremely large surface area and pore volume, have received much attention because of their biomedical application potential. Using MPS NPs for biomedical devices requires the verification of their biocompatibility because the surface area of NPs is one of the most important determinants of toxicity, including the cellular uptake and immune response. We have previously reported that the cytotoxicity and inflammation potential of MPS NPs have been shown to be lower than those of general amorphous colloidal silica (Col) NPs in macrophages, but the low cytotoxicity does not guarantee high biocompatibility in vivo. In this study, we compared the in vivo immunotoxicity of MPS and Col NPs in the mouse model to define the effects of pore structural conditions of silica NPs.Materials and methodsBoth MPS and Col NPs (2, 20, and 50 mg/kg/day) were intraperitoneally administered in female BALB/c mice for 4 weeks, and clinical toxicity, lymphocyte population, serum IgG/IgM levels, and histological changes were examined.ResultsThere was no overt sign of clinical toxicity in either MPS- or Col-treated mice. However, MPS NPs led to significant increases in liver and spleen weight and splenocyte proliferation. Mice treated with MPS NPs showed altered lymphocyte populations (CD3(+), CD45(+), CD4(+), and CD8(+)) in the spleen, increased serum IgG and IgM levels, and histological changes. Despite slight changes in lymphocyte populations in the spleen, Col NPs did not alter other immunological factors.ConclusionThe results indicate that in vivo exposure to MPS NPs caused more damage to systemic immunity than that of Col NPs through the dysregulation of the spleen. The results for in vivo data are inconsistent with those for in vitro data, which show lower cytotoxicity for MPS NPs. These results suggest the importance of verifying biocompatibility both in vitro and in vivo during the design of new nanomaterials.
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Project description:Using a macrophage cell line, we demonstrate the ability of amorphous silica particles to stimulate inflammatory protein secretion and induce cytotoxicity. Whole genome microarray analysis of early gene expression changes induced by 10nm and 500nm particles showed that the magnitude of change for the majority of genes correlated more tightly with particle surface area than either particle mass or number. Gene expression changes that were size-specific were also identified, however the overall biological processes represented by all gene expression changes were nearly identical, irrespective of particle diameter. Our results suggest that on an equivalent nominal surface area basis, common biological modes of action are expected for nano- and supranano-sized silica particles. Experiment Overall Design: RAW 264.7 mouse macrophage cells were treated with two sizes of amorphous silica particles at three doses each for 2 hours. Cells were exposed to 10nm silica at 5 (low), 20 (mid), or 50 (high) ug/ml or 500nm silica at 250 (low), 500 (mid), or 1000 (high) ug/ml in serum-free medium.
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