uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Single-Walled Carbon Nanotubes Inhibit the Cytochrome P450 Enzyme, CYP3A4
Show others and affiliations
2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, 21316Article in journal (Refereed) Published
Abstract [en]

We report a detailed computational and experimental study of the interaction of single-walled carbon nanotubes (SWCNTs) with the drug-metabolizing cytochrome P450 enzyme, CYP3A4. Dose-dependent inhibition of CYP3A4-mediated conversion of the model compound, testosterone, to its major metabolite, 6β-hydroxy testosterone was noted. Evidence for a direct interaction between SWCNTs and CYP3A4 was also provided. The inhibition of enzyme activity was alleviated when SWCNTs were pre-coated with bovine serum albumin. Furthermore, covalent functionalization of SWCNTs with polyethylene glycol (PEG) chains mitigated the inhibition of CYP3A4 enzymatic activity. Molecular dynamics simulations suggested that inhibition of the catalytic activity of CYP3A4 is mainly due to blocking of the exit channel for substrates/products through a complex binding mechanism. This work suggests that SWCNTs could interfere with metabolism of drugs and other xenobiotics and provides a molecular mechanism for this toxicity. Our study also suggests means to reduce this toxicity, eg., by surface modification.

Place, publisher, year, edition, pages
2016. Vol. 6, 21316
National Category
Engineering and Technology
URN: urn:nbn:se:uu:diva-280721DOI: 10.1038/srep21316ISI: 000370493000001OAI: oai:DiVA.org:uu-280721DiVA: diva2:911824
Swedish Research Council for Environment, Agricultural Sciences and Spatial PlanningEU, FP7, Seventh Framework Programme, 310584Swedish Research Council
Available from: 2016-03-14 Created: 2016-03-14 Last updated: 2016-03-30Bibliographically approved

Open Access in DiVA

fulltext(1728 kB)60 downloads
File information
File name FULLTEXT01.pdfFile size 1728 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full texthttp://www.nature.com/articles/srep21316

Search in DiVA

By author/editor
Li, HuLeifer, Klaus
By organisation
Applied Materials Sciences
In the same journal
Scientific Reports
Engineering and Technology

Search outside of DiVA

GoogleGoogle Scholar
Total: 60 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 175 hits
ReferencesLink to record
Permanent link

Direct link