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To fill this gap, the biological response, distribution, and bio\u2010persistence of four different GBMs in mouse lungs up to 28 days after single oropharyngeal aspiration are investigated. None of the GBMs, varying in size (large versus small) and carbon to oxygen ratio as well as thickness (few\u2010layers graphene (FLG) versus thin graphene oxide (GO)), induce a strong pulmonary immune response. However, recruited neutrophils internalize nanosheets better and degrade GBMs faster than macrophages, revealing their crucial role in the elimination of small GBMs. In contrast, large GO sheets induce more damages due to a hindered degradation and long\u2010term persistence in macrophages. Overall, small dimensions appear to be a leading feature in the design of safe GBM pulmonary nanovectors due to an enhanced degradation in phagocytes and a faster clearance from the lungs for small GBMs. Thickness also plays an important role, since decreased material loading in alveolar phagocytes and faster elimination are found for FLGs compared to thinner GOs. These results are important for designing safer\u2010by\u2010design GBMs for biomedical application.<\/jats:p>","DOI":"10.1002\/smll.202301201","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T12:47:36Z","timestamp":1685710056000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Lung Persistence, Biodegradation, and Elimination of Graphene\u2010Based Materials are Predominantly Size\u2010Dependent and Mediated by Alveolar Phagocytes"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9171-9819","authenticated-orcid":false,"given":"Thomas","family":"Loret","sequence":"first","affiliation":[{"name":"Nanomedicine Lab 2.0 School of Biological Sciences Faculty of Biology Medicine and Health The University of Manchester Manchester Academic Health Science Centre  Manchester M13 9PT UK"},{"name":"National Graphene Institute The University of Manchester  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