{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T05:47:54Z","timestamp":1794030474426,"version":"4.8.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373178"],"award-info":[{"award-number":["82373178"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073207"],"award-info":[{"award-number":["82073207"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Nanobiotechnol"],"DOI":"10.1186\/s12951-025-03792-2","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T13:16:07Z","timestamp":1762780567000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Targeting bone marrow adipocyte-driven fatty acid metabolism to overcome drug resistance in lung cancer bone metastasis"],"prefix":"10.1186","volume":"23","author":[{"given":"Jian","family":"Dong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaze","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuoer","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengzhe","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wangjun","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianwen","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"3792_CR1","first-page":"12","volume":"74","author":"RL Siegel","year":"2024","unstructured":"Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74:12\u201349.","journal-title":"CA Cancer J Clin"},{"key":"3792_CR2","first-page":"229","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229\u201363.","journal-title":"CA Cancer J Clin"},{"key":"3792_CR3","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/S0140-6736(16)30958-8","volume":"389","author":"FR Hirsch","year":"2017","unstructured":"Hirsch FR, et al. Lung cancer: current therapies and new targeted treatments. Lancet. 2017;389:299\u2013311.","journal-title":"Lancet"},{"key":"3792_CR4","doi-asserted-by":"publisher","first-page":"439","DOI":"10.21037\/tlcr-20-835","volume":"10","author":"S Wu","year":"2021","unstructured":"Wu S, Pan Y, Mao Y, Chen Y, He Y. Current progress and mechanisms of bone metastasis in lung cancer: a narrative review. Transl Lung Cancer Res. 2021;10:439\u201351.","journal-title":"Transl Lung Cancer Res"},{"key":"3792_CR5","doi-asserted-by":"publisher","first-page":"2099","DOI":"10.1002\/jbmr.3618","volume":"33","author":"J Fornetti","year":"2018","unstructured":"Fornetti J, Welm AL, Stewart SA. Understanding the bone in cancer metastasis. J Bone Miner Res. 2018;33:2099\u2013113.","journal-title":"J Bone Miner Res"},{"key":"3792_CR6","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.lungcan.2014.07.020","volume":"86","author":"M Riihim\u00e4ki","year":"2014","unstructured":"Riihim\u00e4ki M, et al. Metastatic sites and survival in lung cancer. Lung Cancer. 2014;86:78\u201384.","journal-title":"Lung Cancer"},{"key":"3792_CR7","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-020-00105-1","volume":"8","author":"M Wang","year":"2020","unstructured":"Wang M, Xia F, Wei Y, Wei X. Molecular mechanisms and clinical management of cancer bone metastasis. Bone Res. 2020;8:30.","journal-title":"Bone Res"},{"key":"3792_CR8","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1007\/s10555-022-10042-6","volume":"41","author":"M Hernandez","year":"2022","unstructured":"Hernandez M, Shin S, Muller C, Attan\u00e9 C. The role of bone marrow adipocytes in cancer progression: the impact of obesity. Cancer Metastasis Rev. 2022;41:589\u2013605.","journal-title":"Cancer Metastasis Rev"},{"issue":"1","key":"3792_CR9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-61088-3","volume":"16","author":"L Cao","year":"2025","unstructured":"Cao L, et al. Adipocyte-specific Zeb1 downregulation remodels the tumor-associated adipose microenvironment to facilitate female breast cancer progression. Nat Commun. 2025;16(1):6011.","journal-title":"Nat Commun"},{"key":"3792_CR10","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1016\/j.bone.2011.06.032","volume":"50","author":"B Lecka-Czernik","year":"2012","unstructured":"Lecka-Czernik B. Marrow fat metabolism is linked to the systemic energy metabolism. Bone. 2012;50:534\u20139.","journal-title":"Bone"},{"key":"3792_CR11","doi-asserted-by":"crossref","unstructured":", He J, Yang J. Bone marrow microenvironment: roles and therapeutic implications in obesity-associated cancer. Trends Cancer .2023; 9(7): 566-577.","DOI":"10.1016\/j.trecan.2023.03.007"},{"key":"3792_CR12","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1002\/j.2040-4603.2018.tb00007.x","volume":"8","author":"FJA de Paula","year":"2017","unstructured":"de Paula FJA, Rosen CJ. Structure and function of bone marrow adipocytes. Compr Physiol. 2017;8:315\u201349.","journal-title":"Compr Physiol"},{"key":"3792_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00685","volume":"9","author":"GCM Evangelista","year":"2019","unstructured":"Evangelista GCM, et al. 4T1 mammary carcinoma colonization of metastatic niches is accelerated by obesity. Front Oncol. 2019;9:685.","journal-title":"Front Oncol"},{"key":"3792_CR14","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2024.167325","volume":"1870","author":"R Roy","year":"2024","unstructured":"Roy R, et al. Mammary adipocytes promote breast tumor cell invasion and angiogenesis in the context of menopause and obesity. Biochim Biophys Acta Mol Basis Dis. 2024;1870:167325.","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"3792_CR15","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1038\/s41580-019-0123-5","volume":"20","author":"J Zhu","year":"2019","unstructured":"Zhu J, Thompson CB. Metabolic regulation of cell growth and proliferation. Nat Rev Mol Cell Biol. 2019;20:436\u201350.","journal-title":"Nat Rev Mol Cell Biol"},{"key":"3792_CR16","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.addr.2020.07.013","volume":"159","author":"LM Butler","year":"2020","unstructured":"Butler LM, et al. Lipids and cancer: emerging roles in pathogenesis, diagnosis and therapeutic intervention. Adv Drug Deliv Rev. 2020;159:245\u201393.","journal-title":"Adv Drug Deliv Rev"},{"key":"3792_CR17","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/s41416-019-0650-z","volume":"122","author":"N Koundouros","year":"2020","unstructured":"Koundouros N, Poulogiannis G. Reprogramming of fatty acid metabolism in cancer. Br J Cancer. 2020;122:4\u201322.","journal-title":"Br J Cancer"},{"key":"3792_CR18","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/s41568-019-0216-7","volume":"20","author":"G Hoxhaj","year":"2020","unstructured":"Hoxhaj G, Manning BD. The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism. Nat Rev Cancer. 2020;20:74\u201388.","journal-title":"Nat Rev Cancer"},{"key":"3792_CR19","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1194\/jlr.M088559","volume":"60","author":"J Roy","year":"2019","unstructured":"Roy J, Dibaeinia P, Fan TM, Sinha S, Das A. Global analysis of osteosarcoma lipidomes reveal altered lipid profiles in metastatic versus nonmetastatic cells. J Lipid Res. 2019;60:375\u201387.","journal-title":"J Lipid Res"},{"key":"3792_CR20","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1038\/s41568-021-00388-4","volume":"21","author":"AJ Hoy","year":"2021","unstructured":"Hoy AJ, Nagarajan SR, Butler LM. Tumour fatty acid metabolism in the context of therapy resistance and obesity. Nat Rev Cancer. 2021;21:753\u201366.","journal-title":"Nat Rev Cancer"},{"key":"3792_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05930-w","volume":"14","author":"Z Chen","year":"2023","unstructured":"Chen Z, et al. Ferroptosis as a potential target for cancer therapy. Cell Death Dis. 2023;14:460.","journal-title":"Cell Death Dis"},{"issue":"2","key":"3792_CR22","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/s41573-021-00339-6","volume":"21","author":"ZE Stine","year":"2022","unstructured":"Stine ZE, Schug ZT, Salvino JM, Dang CV. Targeting cancer metabolism in the era of precision oncology. Nat Rev Drug Discov. 2022;21(2):141\u201362.","journal-title":"Nat Rev Drug Discov"},{"key":"3792_CR23","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1016\/j.cmet.2023.07.006","volume":"35","author":"Y Xiao","year":"2023","unstructured":"Xiao Y, et al. Emerging therapies in cancer metabolism. Cell Metab. 2023;35:1283\u2013303.","journal-title":"Cell Metab"},{"key":"3792_CR24","doi-asserted-by":"crossref","unstructured":"Li X, Sun T, Jiang C. Intelligent delivery systems in tumor metabolism regulation: exploring the path ahead. Advanced Materials. 2024; 36(11): 2309582.","DOI":"10.1002\/adma.202309582"},{"key":"3792_CR25","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/nrc.2016.44","volume":"16","author":"PI Croucher","year":"2016","unstructured":"Croucher PI, McDonald MM, Martin TJ. Bone metastasis: the importance of the neighbourhood. Nat Rev Cancer. 2016;16:373\u201386.","journal-title":"Nat Rev Cancer"},{"key":"3792_CR26","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22168847","author":"F Tie","year":"2021","unstructured":"Tie F, et al. Kaempferol and kaempferide attenuate oleic acid-induced lipid accumulation and oxidative stress in HepG2 cells. Int J Mol Sci. 2021. https:\/\/doi.org\/10.3390\/ijms22168847.","journal-title":"Int J Mol Sci"},{"key":"3792_CR27","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115113","volume":"165","author":"N Li","year":"2023","unstructured":"Li N, et al. Kaempferol attenuates nonalcoholic fatty liver disease in type 2 diabetic mice via the Sirt1\/AMPK signaling pathway. Biomed Pharmacother. 2023;165:115113.","journal-title":"Biomed Pharmacother"},{"key":"3792_CR28","doi-asserted-by":"crossref","unstructured":"Rocha CRR, Silva MM, Quinet A, Cabral-Neto JB, Menck CF. M. DNA repair pathways and cisplatin resistance: an intimate relationship. Clinics 73, e478s (2018).","DOI":"10.6061\/clinics\/2018\/e478s"},{"key":"3792_CR29","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22158199","volume":"22","author":"RC Kiss","year":"2021","unstructured":"Kiss RC, Xia F, Acklin S. Targeting. DNA damage response and repair to enhance therapeutic index in Cisplatin-based cancer treatment. Int J Mol Sci. 2021;22:8199.","journal-title":"Int J Mol Sci"},{"issue":"1","key":"3792_CR30","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1007\/s10555-024-10170-1","volume":"43","author":"R Vishwa","year":"2024","unstructured":"Vishwa R, et al. Lipid metabolism and its implications in tumor cell plasticity and drug resistance: what we learned thus far? Cancer Metastasis Rev. 2024;43(1):293\u2013319.","journal-title":"Cancer Metastasis Rev"},{"key":"3792_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05968-w","volume":"14","author":"S Yang","year":"2023","unstructured":"Yang S, et al. Fatty acid oxidation facilitates DNA double-strand break repair by promoting PARP1 acetylation. Cell Death Dis. 2023;14:435.","journal-title":"Cell Death Dis"},{"key":"3792_CR32","doi-asserted-by":"crossref","unstructured":"Fanale D, Amodeo V, Caruso S. The Interplay between Metabolism, PPAR Signaling Pathway, and Cancer. PPAR Res. 2017, 1830626 (2017).","DOI":"10.1155\/2017\/1830626"},{"key":"3792_CR33","doi-asserted-by":"crossref","unstructured":"Wu X et al. FASN regulates cellular response to genotoxic treatments by increasing PARP-1 expression and DNA repair activity via NF-\u03baB and SP1. Proc. Natl. Acad. Sci. 113, (2016).","DOI":"10.1073\/pnas.1609934113"},{"key":"3792_CR34","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/j.jbior.2013.09.004","volume":"54","author":"X Wu","year":"2014","unstructured":"Wu X, Qin L, Fako V, Zhang J-T. Molecular mechanisms of fatty acid synthase (FASN)-mediated resistance to anti-cancer treatments. Adv Biol Regul. 2014;54:214\u201321.","journal-title":"Adv Biol Regul"},{"key":"3792_CR35","first-page":"1066","volume":"182","author":"B Li","year":"2020","unstructured":"Li B, Hao J, Zeng J, Sauter ER, SnapShot. FABP Funct Cell. 2020;182:1066\u2013e10661.","journal-title":"FABP Funct Cell"},{"key":"3792_CR36","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-12-280","volume":"12","author":"J Relat","year":"2012","unstructured":"Relat J, et al. Different fatty acid metabolism effects of (-)-epigallocatechin-3-gallate and C75 in adenocarcinoma lung cancer. BMC Cancer. 2012;12:280.","journal-title":"BMC Cancer"},{"key":"3792_CR37","doi-asserted-by":"publisher","first-page":"3561","DOI":"10.2147\/IJN.S133787","volume":"12","author":"J Liu","year":"2017","unstructured":"Liu J, et al. Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (\u03b5-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone. Int J Nanomed. 2017;12:3561\u201375.","journal-title":"Int J Nanomed"},{"key":"3792_CR38","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/j.ijpharm.2014.08.067","volume":"475","author":"T Jiang","year":"2014","unstructured":"Jiang T, et al. Poly aspartic acid peptide-linked PLGA based nanoscale particles: potential for bone-targeting drug delivery applications. Int J Pharm. 2014;475:547\u201357.","journal-title":"Int J Pharm"},{"key":"3792_CR39","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3390\/polym3010010","volume":"3","author":"TT Thula","year":"2011","unstructured":"Thula TT, et al. Mimicking the nanostructure of bone: comparison of polymeric process-directing agents. Polymers. 2011;3:10\u201335.","journal-title":"Polymers"},{"key":"3792_CR40","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202412730","author":"Y Xing","year":"2024","unstructured":"Xing Y, et al. Lysosome targeted nanoparticle aggregation reverses immunosuppressive tumor microenvironment for cancer immunotherapy. Adv Mater. 2024. https:\/\/doi.org\/10.1002\/adma.202412730.","journal-title":"Adv Mater"},{"key":"3792_CR41","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1016\/j.plipres.2013.05.001","volume":"52","author":"JP Slotte","year":"2013","unstructured":"Slotte JP. Biological functions of sphingomyelins. Prog Lipid Res. 2013;52:424\u201337.","journal-title":"Prog Lipid Res"},{"key":"3792_CR42","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1194\/jlr.M033811","volume":"54","author":"H Liu","year":"2013","unstructured":"Liu H, et al. Fatty acid synthase causes drug resistance by inhibiting TNF-\u03b1 and ceramide production. J Lipid Res. 2013;54:776\u201385.","journal-title":"J Lipid Res"},{"key":"3792_CR43","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abq6288","volume":"15","author":"KM Eyme","year":"2023","unstructured":"Eyme KM, et al. Targeting de novo lipid synthesis induces lipotoxicity and impairs DNA damage repair in glioblastoma mouse models. Sci Transl Med. 2023;15:eabq6288.","journal-title":"Sci Transl Med"},{"key":"3792_CR44","doi-asserted-by":"publisher","first-page":"2621","DOI":"10.1080\/15548627.2023.2218764","volume":"19","author":"Y Xie","year":"2023","unstructured":"Xie Y, Kang R, Klionsky DJ, Tang D. GPX4 in cell death, autophagy, and disease. Autophagy. 2023;19:2621\u201338.","journal-title":"Autophagy"}],"container-title":["Journal of Nanobiotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12951-025-03792-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12951-025-03792-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12951-025-03792-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T18:15:48Z","timestamp":1762884948000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnanobiotechnology.biomedcentral.com\/articles\/10.1186\/s12951-025-03792-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,10]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3792"],"URL":"https:\/\/doi.org\/10.1186\/s12951-025-03792-2","relation":{},"ISSN":["1477-3155"],"issn-type":[{"value":"1477-3155","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,10]]},"assertion":[{"value":"18 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"709"}}