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Functionalized carbon nanotubes as immunomodulator systems

Paper ID Volume ID Publish Year Pages File Format Full-Text
6117 463 2013 9 PDF Available
Title
Functionalized carbon nanotubes as immunomodulator systems
Abstract

In view of the broad potential biomedical applications of carbon nanotubes (CNTs) different studies were performed to assess their effect on the immune system. However, the work performed to date was able to give a restricted view looking only at some activation markers and cytokine expression. The immune system is rarely limited to few molecule interactions being instead always a balance of switching several genes on and off. Whole genome expression (microarray) is a technology able to give the full picture on genome expression. Here we describe a microarray genome-wide study on Jurkat cells, a T lymphocyte cell line, and THP1, a monocytic cell line, representative of both types of immune response, the adaptive and innate, respectively. Since any structure or molecule modification may lead to very different immune reactions, we treated the two cell lines with four types of functionalized multi-walled CNTs that differ in terms of functionalization and diameter. After having assessed the internalization and the lack of toxicity of CNTs in both cell types, we used the Affymetrix technology to analyze the expression of about 32,000 transcripts. Three of the tested nanotubes (i.e., ox-MWCNT-1, ox-MWCNT-NH3+-1, and ox-MWCNT-NH3+-2) activated immune-related pathways in monocytes but not in T cells. In view of these charateristics they were named as monocyte activating CNTs (MA-CNTs). Molecular pathways upregulated by MA-CNTs included IL6, CD40, dendritic cell maturation, tumor necrosis factor-(TNF)-α/TNFR1-2, NFKB signaling and T helper 1 chemokine pathways (CXCR3 and CCR5 ligand pathways). These pathways are commonly activated during acute inflammatory processes as those associated with immune-mediated tumor rejection and pathogen clearance. One of them (i.e., ox-MWCNT-2) downregulated genes associated with ribosomal proteins in both monocytes and T cells. We validated our findings at gene expression level by performing real-time PCR assessing the most highly modulated genes in monocytes. To confirm the results at protein level, the secretion of IL1β, TNFα, IL6 and IL10 by THP1 and primary monocytes was assessed by ELISA, corroborating gene-expression data. Our results provide new insights into the whole gene expression modulation by different CNTs on immune cells. Considering the well known drug carrier ability of CNTs, our findings demonstrate that MA-CNTs here behave as cell specific immunostimulatory systems, giving very interesting future perspectives for their application also as immunotherapeutic agents and/or vaccine adjuvants.

Keywords
Nanomedicine; Carbon nanomaterials; Immune system; Gene expression; Microarrays; Cytokines
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 18, June 2013, Pages 4395–4403
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