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However, the fate of the delivery system itself remains to be understood. In this study 2 kDa PEG\u2010modified single\u2010walled carbon nanotubes (PNTs) are synthesized, and trafficking and degradation following intra\u2010articular injection into the knee\u2010joint of healthy mice are studied. Using confocal Raman microspectroscopy, PNTs can be imaged in the knee\u2010joint 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\u2010rich 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\u20105) and macrophage (RAW264.7) cell lines, biodegradation of PNTs in activated, nitric oxide (NO)\u2010producing 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\u2010free degradation of PNTs upon incubation with the peroxynitrite\u2010generating compound, SIN\u20101 is demonstrated. The present study paves the way for the use of PNTs as delivery systems in the treatment of diseases of the joint.<\/jats:p>","DOI":"10.1002\/adhm.201700916","type":"journal-article","created":{"date-parts":[[2018,1,15]],"date-time":"2018-01-15T05:54:38Z","timestamp":1515995678000},"source":"Crossref","is-referenced-by-count":19,"title":["Nitric Oxide Dependent Degradation of Polyethylene Glycol\u2010Modified Single\u2010Walled Carbon Nanotubes: Implications for Intra\u2010Articular Delivery"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9393-9807","authenticated-orcid":false,"given":"Kunal","family":"Bhattacharya","sequence":"first","affiliation":[{"name":"Nanosafety &amp; Nanomedicine Laboratory\u2010NNL Division of Molecular Toxicology Institute of Environmental Medicine Karolinska Institutet  171 77 Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiano","family":"Sacchetti","sequence":"additional","affiliation":[{"name":"Division of Cellular Biology La Jolla Institute for Allergy and Immunology  La Jolla CA 92037 USA"},{"name":"Department of Medicine, and Clinical and Translational Research Institute University of California San Diego  La Jolla CA 92037 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro M.","family":"Costa","sequence":"additional","affiliation":[{"name":"Nanosafety &amp; 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