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The systemic toxicity of positively charged lipid nanoparticles and the role of Toll-like receptor 4 in immune activation

Paper ID Volume ID Publish Year Pages File Format Full-Text
8723 603 2010 9 PDF Available
Title
The systemic toxicity of positively charged lipid nanoparticles and the role of Toll-like receptor 4 in immune activation
Abstract

Delivery of nucleic acids with positively charged lipid nanoparticles ((+)NPs) is widely used as research reagents and potentially for therapeutics due to their ability to deliver nucleic acids into the cell cytoplasm. However, in most reports little attention has been made to their toxic effects. In the present study, we performed comprehensive analyses of the potential toxicity associated with (+)NPs. Mice treated with (+)NPs showed increased liver enzyme release and body weight loss compared to mice treated with neutral or negatively charged NPs ((−)NPs), suggesting hepatotoxicity. Intravenous administration of (+)NPs induced interferon type I response and elevated mRNA levels of interferon responsive genes 15–25-fold higher than neutral and (−)NPs in different subsets of leukocytes. Moreover, treatment with (+)NPs provoked a dramatic pro-inflammatory response by inducing Th1 cytokines expression (IL-2, IFN γ and TNF α) 10–75-fold higher than treatment with control particles. Finally, we showed that activation of TLR4 might serve as the underlying mechanism for induction of an immune response when (+)NPs are used. These results suggest that a careful attention must be made when different types of (+)NPs are being developed as nanotherapeutics.

Keywords
Lipid-based nanoparticles; Immune activation; Interferon response; Cytokine induction; TLR4
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The systemic toxicity of positively charged lipid nanoparticles and the role of Toll-like receptor 4 in immune activation
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 26, September 2010, Pages 6867–6875
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us