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Here, we developed an integrated label\u2010free mass spectrometry imaging (MSI) platform to investigate BP's in vivo distribution, transformation, clearance, and metabolism in tumor\u2010bearing mice. We detected BPs and related nitrogen\/oxygen\u2010containing phosphorus (P) clusters in six organs and tumor tissues, revealing distinctive tissue distributions. BP and its degradation products primarily accumulated in the liver and spleen, with the liver showing a radial distribution pattern around hepatic lobules. Notably, BP and related clusters can cross the blood\u2013brain barrier into brain parenchyma. We further establish the in vivo transformation and metabolic pathways of BPs. Cellular experiments confirmed that nitric oxide synthase (NOS)\u2010mediated nitric oxide (NO) generation drives BP nitridation during its transformation and metabolism under physiological conditions. This work not only provides vital information for biomedical applications of BP, but also establishes a platform for understanding in vivo translocation and transformation of nanomaterials, aiding their biosafety and health impact assessments.<\/jats:p>","DOI":"10.1002\/adhm.71824","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T03:36:31Z","timestamp":1791776191000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mass Spectrometry Imaging Reveals Biodistribution and Biotransformation of Black Phosphorus"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1136-7599","authenticated-orcid":false,"given":"Xiu","family":"Huang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Environmental Chemistry and Toxicology Research Center for Eco\u2010Environmental Sciences Chinese Academy of Sciences  Beijing China"},{"name":"West China School of Public Health and West China Fourth Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Environmental Chemistry and Toxicology Research Center for Eco\u2010Environmental Sciences Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinwei","family":"Liu","sequence":"additional","affiliation":[{"name":"West China School of Public Health and West China Fourth Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhong","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Environmental Chemistry and Toxicology Research Center for Eco\u2010Environmental Sciences Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Environmental Chemistry and Toxicology Research Center for Eco\u2010Environmental Sciences Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1870-6194","authenticated-orcid":false,"given":"Hua","family":"Qin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Environmental Chemistry and Toxicology Research Center for Eco\u2010Environmental Sciences Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5220-7009","authenticated-orcid":false,"given":"Guangbo","family":"Qu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Environmental Chemistry and Toxicology Research Center for Eco\u2010Environmental Sciences Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8525-7961","authenticated-orcid":false,"given":"Qian","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Environmental Chemistry and Toxicology Research Center for Eco\u2010Environmental Sciences Chinese Academy of Sciences  Beijing China"},{"name":"College of Resources and Environment University of Chinese Academy of Sciences  Beijing China"},{"name":"Institute of Environment and Health Jianghan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guibin","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Environmental Chemistry and Toxicology Research Center for Eco\u2010Environmental Sciences Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/nnano.2014.35","article-title":"Black Phosphorus Field\u2010Effect Transistors","volume":"9","author":"Li L.","year":"2014","journal-title":"Nature Nanotechnology"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"4475","DOI":"10.1038\/ncomms5475","article-title":"High\u2010Mobility Transport Anisotropy and Linear Dichroism in Few\u2010Layer Black Phosphorus","volume":"5","author":"Qiao J.","year":"2014","journal-title":"Nature Communications"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"4458","DOI":"10.1038\/ncomms5458","article-title":"Rediscovering Black Phosphorus as an Anisotropic Layered Material for Optoelectronics and Electronics","volume":"5","author":"Xia F.","year":"2014","journal-title":"Nature 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W.","year":"2021","journal-title":"Drug Delivery and Translational Research"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsabm.8b00150"},{"key":"e_1_2_10_56_1","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.3390\/bios12111009","article-title":"2D Hetero\u2010Nanoconstructs of Black Phosphorus for Breast Cancer Theragnosis: Technological Advancements","volume":"12","author":"Soman S.","year":"2022","journal-title":"Biosensors"},{"key":"e_1_2_10_57_1","doi-asserted-by":"crossref","DOI":"10.1093\/rb\/rbae046","article-title":"Polydopamine\u2010Modified Black Phosphorus Nanosheet Drug Delivery System for the Treatment of Ischemic Stroke","volume":"11","author":"Yin S.","year":"2024","journal-title":"Regenerative Biomaterials"},{"key":"e_1_2_10_58_1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.3390\/pharmaceutics16020273","article-title":"Harnessing the Potential of PLGA Nanoparticles for Enhanced Bone Regeneration","volume":"16","author":"Hassan M.","year":"2024","journal-title":"Pharmaceutics"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.5b07712"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.71824","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adhm.71824","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.71824","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T03:36:36Z","timestamp":1791776196000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.71824"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,11]]},"references-count":58,"alternative-id":["10.1002\/adhm.71824"],"URL":"https:\/\/doi.org\/10.1002\/adhm.71824","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,11]]},"assertion":[{"value":"2026-03-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71824"}}