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Nitric Oxide Dependent Degradation of Polyethylene Glycol-Modified Single-Walled Carbon Nanotubes: Implications for Intra-Articular Delivery
Karolinska Institutet, Sweden.
La Jolla Institute for Allergy and Immunology, USA ; University of California San Diego, USA..
Karolinska Institutet, Sweden.
RISE - Research Institutes of Sweden, Bioscience and Materials, Chemistry and Materials.ORCID iD: 0000-0002-4697-9192
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2018 (English)In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659Article in journal (Refereed) In press
Abstract [en]

Polyethylene glycol (PEG)-modified carbon nanotubes have been successfully employed for intra-articular delivery in mice without systemic or local toxicity. However, the fate of the delivery system itself remains to be understood. In this study 2 kDa PEG-modified single-walled carbon nanotubes (PNTs) are synthesized, and trafficking and degradation following intra-articular injection into the knee-joint of healthy mice are studied. Using confocal Raman microspectroscopy, PNTs can be imaged in the knee-joint and are found to either egress from the synovial cavity or undergo biodegradation over a period of 3 weeks. Raman analysis discloses that PNTs are oxidatively degraded mainly in the chondrocyte-rich cartilage and meniscus regions while PNTs can also be detected in the synovial membrane regions, where macrophages can be found. Furthermore, using murine chondrocyte (ATDC-5) and macrophage (RAW264.7) cell lines, biodegradation of PNTs in activated, nitric oxide (NO)-producing chondrocytes, which is blocked upon pharmacological inhibition of inducible nitric oxide synthase (iNOS), can be shown. Biodegradation of PNTs in macrophages is also noted, but after a longer period of incubation. Finally, cell-free degradation of PNTs upon incubation with the peroxynitrite-generating compound, SIN-1 is demonstrated. The present study paves the way for the use of PNTs as delivery systems in the treatment of diseases of the joint.

Place, publisher, year, edition, pages
2018.
Keywords [en]
Biodegradation, Carbon nanotubes, Chondrocytes, Intra-articular injection, Macrophages
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:ri:diva-33271DOI: 10.1002/adhm.201700916Scopus ID: 2-s2.0-85040665656OAI: oai:DiVA.org:ri-33271DiVA, id: diva2:1181968
Available from: 2018-02-12 Created: 2018-02-12 Last updated: 2018-03-16Bibliographically approved

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Sommertune, Jens

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