Aggressive penetration of nanomaterials in different spheres of our life from novel technologies to a plethora of consumer products, raises concerns about their possible adverse effects on public health. Several studies report that nanotubes cause lung toxicity. With increase in day-to-day applications of carbon nanotubes, particulate exposure either under occupational or environmental settings is inevitable. In the classic inflammatory response to nanotubes, emigration of neutrophils (PMNs) followed by macrophages into sites of particle deposition has been observed. The major role of the cells is to phagocytoze and promotes particulate clearance and the clearance might be essentially dependent on effective recognition. Carbon nanotubes are not effectively recognized by professional phagocytes and delayed clearance of particles within the lung parenchyma can thus be majorly attributed to impaired phagocytosis or deficiency in components involving their effective degradation. We in our research coated nanotubes with biomolecules to promote recognition, uptake and biodegradation by professional phagocytes. Coating nanotubes with eat-me-phospholipid signal, phosphatidylserine proved to be an effective strategy for targeting particles to professional phagocytes, specifically macrophages both in vitro and in vivo. However, opsonization of nanotubes made them competent for both macrophages and neutrophils. This targeting also enhanced the biodegradation in neutrophils and to a lesser extent in macrophages via action of myeloperoxidase and its potent oxidants whose critical role in biodegradation was delineated in cell free based in vitro studies. Further, in vivo experiments using wild type and myeloperoxidase null mice showed a significantly lower degree of biodegradation and particle elimination in latter animal type, underscoring the role of neutrophil peroxidase in biodegrading carbon nanotubes. Using contemporary techniques- confocal, transmission and scanning electron microscopy, Vis-NIR and Raman spectroscopy, we evaluated the hypothesis. Taken together, the results from the doctoral work suggest that targeting of nanotubes to professional phagocytes can be achieved by coating with certain biomolecules and this targeting can reduce the biopersistence and inflammation associated due to the presence of otherwise relatively biodurable nanotubes in biological ambience. The dissertation also foresees functionalization of nanotubes as a strategy to combat potential toxic effects of nanotubes which pose potential risk to the public health.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-07262010-063543 |
| Date | 27 September 2010 |
| Creators | Konduru, Nagarjun Venkata |
| Contributors | Dr. Hulya Bayir, Dr. James Fabisiak, Dr. Alexander Star, Dr. Valerian E. Kagan |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-07262010-063543/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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