Journal
NANOSCALE RESEARCH LETTERS
Volume 9, Issue -, Pages -Publisher
SPRINGER
DOI: 10.1186/1556-276X-9-651
Keywords
Nanomaterials; Silica nanoparticles; Size; Surface modification; CYP3A4; Human liver microsomes
Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT)
- Japan Society for the Promotion of Science (JSPS)
- Health Labour Sciences Research Grants from the Ministry of Health, Labour and Welfare of Japan (MHLW)
- Takeda Science Foundation
- Research Foundation for Pharmaceutical Sciences
- Japan Food Chemical Research Foundation
- Urakami Foundation
- Uehara Memorial Foundation
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Because of their useful chemical and physical properties, nanomaterials are widely used around the world - for example, as additives in food and medicines - and such uses are expected to become more prevalent in the future. Therefore, collecting information about the effects of nanomaterials on metabolic enzymes is important. Here, we examined the effects of amorphous silica particles with various sizes and surface modifications on cytochrome P450 3A4 (CYP3A4) activity by means of two different in vitro assays. Silica nanoparticles with diameters of 30 and 70 nm (nSP30 and nSP70, respectively) tended to inhibit CYP3A4 activity in human liver microsomes (HLMs), but the inhibitory activity of both types of nanoparticles was decreased by carboxyl modification. In contrast, amine-modified nSP70 activated CYP3A4 activity. In HepG2 cells, nSP30 inhibited CYP3A4 activity more strongly than the larger silica particles did. Taken together, these results suggest that the size and surface characteristics of the silica particles determined their effects on CYP3A4 activity and that it may be possible to develop silica particles that do not have undesirable effects on metabolic enzymes by altering their size and surface characteristics.
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