{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:10:15Z","timestamp":1790727015860,"version":"4.1.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T00:00:00Z","timestamp":1614211200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T00:00:00Z","timestamp":1614211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770070"],"award-info":[{"award-number":["81770070"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010229","name":"Natural Science Foundation of Tianjin Municipal Science and Technology Commission","doi-asserted-by":"publisher","award":["20JCYBJC00040"],"award-info":[{"award-number":["20JCYBJC00040"]}],"id":[{"id":"10.13039\/501100010229","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013285","name":"Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning","doi-asserted-by":"publisher","award":["TP2016014"],"award-info":[{"award-number":["TP2016014"]}],"id":[{"id":"10.13039\/501100013285","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003395","name":"Shanghai Municipal Education Commission","doi-asserted-by":"publisher","award":["20171923"],"award-info":[{"award-number":["20171923"]}],"id":[{"id":"10.13039\/501100003395","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Nanobiotechnol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Uncontrolled inflammation is a central problem for many respiratory diseases. The development of potent, targeted anti-inflammatory therapies to reduce lung inflammation and re-establish the homeostasis in the respiratory tract is still a challenge. Previously, we developed a unique anti-inflammatory nanodrug, P12 (made of hexapeptides and gold nanoparticles), which can attenuate Toll-like receptor-mediated inflammatory responses in macrophages. However, the effect of the administration route on its therapeutic efficacy and tissue distribution remained to be defined.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In this study, we systematically compared the effects of three different administration routes [the intratracheal (i.t.), intravenous (i.v.) and intraperitoneal (i.p.)] on the therapeutic activity, biodistribution and pulmonary cell targeting features of P12. Using the LPS-induced ALI mouse model, we found that the local administration route via i.t. instillation was superior in reducing lung inflammation than the other two routes even treated with a lower concentration of P12. Further studies on nanoparticle biodistribution showed that the i.t. administration led to more accumulation of P12 in the lungs but less in the liver and other organs; however, the i.v. and i.p. administration resulted in more nanoparticle accumulation in the liver and lymph nodes, respectively, but less in the lungs. Such a lung favorable distribution was also determined by the unique surface chemistry of P12. Furthermore, the inflammatory condition in the lung could decrease the accumulation of nanoparticles in the lung and liver, while increasing their distribution in the\u00a0spleen and heart. Interestingly, the i.t. administration route helped the nanoparticles specifically target the lung macrophages, whereas the other two administration routes did not.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>The i.t. administration is better for treating ALI using nanodevices as it enhances the bioavailability and efficacy of the nanodrugs in the target cells of the lung and reduces the potential systematic side effects.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12951-021-00803-w","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T11:04:41Z","timestamp":1614251081000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Administration route governs the therapeutic efficacy, biodistribution and macrophage targeting of anti-inflammatory nanoparticles in the lung"],"prefix":"10.1186","volume":"19","author":[{"given":"Lu","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafei","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiali","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liya","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiameng","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huasheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aihua","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,25]]},"reference":[{"issue":"1","key":"803_CR1","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1038\/ni.3052","volume":"16","author":"M Kopf","year":"2015","unstructured":"Kopf M, Schneider C, Nobs SP. The development and function of lung-resident macrophages and dendritic cells. Nat Immunol. 2015;16(1):36\u201344.","journal-title":"Nat Immunol"},{"issue":"56","key":"803_CR2","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1159\/000487057","volume":"10","author":"D Hartl","year":"2018","unstructured":"Hartl D, Tirouvanziam R, Laval J, Greene CM, Habiel D, Sharma L, Yildirim AO, Dela Cruz CS, Hogaboam CM. Innate immunity of the lung: from basic mechanisms to translational medicine. J Innate Immun. 2018;10(56):487\u2013501.","journal-title":"J Innate Immun"},{"issue":"4","key":"803_CR3","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1007\/s00281-016-0558-0","volume":"38","author":"AH Newton","year":"2016","unstructured":"Newton AH, Cardani A, Braciale TJ. The host immune response in respiratory virus infection: balancing virus clearance and immunopathology. Semin Immunopathol. 2016;38(4):471\u201382.","journal-title":"Semin Immunopathol"},{"issue":"1","key":"803_CR4","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1007\/s00011-018-1191-2","volume":"68","author":"P Aghasafari","year":"2019","unstructured":"Aghasafari P, George U, Pidaparti R. A review of inflammatory mechanism in airway diseases. Inflamm Res. 2019;68(1):59\u201374.","journal-title":"Inflamm Res"},{"issue":"3","key":"803_CR5","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1152\/physrev.00032.2017","volume":"98","author":"LJ Quinton","year":"2018","unstructured":"Quinton LJ, Walkey AJ, Mizgerd JP. Integrative physiology of pneumonia. Physiol Rev. 2018;98(3):1417\u201364.","journal-title":"Physiol Rev"},{"issue":"6","key":"803_CR6","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1038\/s41577-020-0311-8","volume":"20","author":"MZ Tay","year":"2020","unstructured":"Tay MZ, Poh CM, Renia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020;20(6):363\u201374.","journal-title":"Nat Rev Immunol"},{"issue":"13","key":"803_CR7","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1042\/CS20160487","volume":"131","author":"PJ Barnes","year":"2017","unstructured":"Barnes PJ. Cellular and molecular mechanisms of asthma and COPD. Clin Sci. 2017;131(13):1541\u201358.","journal-title":"Clin Sci"},{"issue":"5","key":"803_CR8","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1007\/s00281-017-0629-x","volume":"39","author":"R Channappanavar","year":"2017","unstructured":"Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017;39(5):529\u201339.","journal-title":"Semin Immunopathol"},{"key":"803_CR9","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1196\/annals.1321.004","volume":"1024","author":"GU Meduri","year":"2004","unstructured":"Meduri GU, Yates CR. Systemic inflammation-associated glucocorticoid resistance and outcome of ARDS. Ann N Y Acad Sci. 2004;1024:24\u201353.","journal-title":"Ann N Y Acad Sci"},{"key":"803_CR10","doi-asserted-by":"publisher","first-page":"69","DOI":"10.3389\/fped.2016.00069","volume":"4","author":"GU Meduri","year":"2016","unstructured":"Meduri GU, Schwingshackl A, Hermans G. Prolonged glucocorticoid treatment in ARDS: impact on intensive care unit-acquired weakness. Front Pediatr. 2016;4:69.","journal-title":"Front Pediatr"},{"issue":"5 Suppl 35","key":"803_CR11","first-page":"S77","volume":"22","author":"HB Townsend","year":"2004","unstructured":"Townsend HB, Saag KG. Glucocorticoid use in rheumatoid arthritis: benefits, mechanisms, and risks. Clin Exp Rheumatol. 2004;22(5 Suppl 35):S77-82.","journal-title":"Clin Exp Rheumatol"},{"issue":"6","key":"803_CR12","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1021\/acs.accounts.9b00053","volume":"52","author":"JT Buchman","year":"2019","unstructured":"Buchman JT, Hudson-Smith NV, Landy KM, Haynes CL. Understanding nanoparticle toxicity mechanisms to inform redesign strategies to reduce environmental impact. Accounts Chem Res. 2019;52(6):1632\u201342.","journal-title":"Accounts Chem Res"},{"issue":"11","key":"803_CR13","doi-asserted-by":"publisher","first-page":"13015","DOI":"10.1021\/acsnano.9b05679","volume":"13","author":"YX Tang","year":"2019","unstructured":"Tang YX, Wang XY, Li J, Nie Y, Liao GJ, Yu Y, Li C. Overcoming the reticuloendothelial system barrier to drug delivery with a \u201cDon\u2019t-Eat-Us\u201d strategy. ACS Nano. 2019;13(11):13015\u201326.","journal-title":"ACS Nano"},{"key":"803_CR14","doi-asserted-by":"publisher","DOI":"10.1038\/natrevmats.2016.14","author":"S Wilhelm","year":"2016","unstructured":"Wilhelm S, Tavares AJ, Dai Q, Ohta S, Audet J, Dvorak HF, Chan WCW. Analysis of nanoparticle delivery to tumours. Nat Rev Mater. 2016. https:\/\/doi.org\/10.1038\/natrevmats.2016.14.","journal-title":"Nat Rev Mater"},{"issue":"41","key":"803_CR15","doi-asserted-by":"publisher","first-page":"9643","DOI":"10.1002\/anie.201102911","volume":"50","author":"H Yang","year":"2011","unstructured":"Yang H, Fung SY, Liu M. Programming the cellular uptake of physiologically stable peptide-gold nanoparticle hybrids with single amino acids. Angew Chem Int Ed Engl. 2011;50(41):9643\u20136.","journal-title":"Angew Chem Int Ed Engl"},{"issue":"7","key":"803_CR16","doi-asserted-by":"publisher","first-page":"6774","DOI":"10.1021\/nn505634h","volume":"9","author":"H Yang","year":"2015","unstructured":"Yang H, Fung SY, Xu S, Sutherland DP, Kollmann TR, Liu M, Turvey SE. Amino acid-dependent attenuation of toll-like receptor signaling by peptide-gold nanoparticle hybrids. ACS Nano. 2015;9(7):6774\u201384.","journal-title":"ACS Nano"},{"key":"803_CR17","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.biomaterials.2016.09.032","volume":"111","author":"H Yang","year":"2016","unstructured":"Yang H, Kozicky L, Saferali A, Fung SY, Afacan N, Cai B, Falsafi R, Gill E, Liu M, Kollmann TR, Hancock RE, Sly LM, Turvey SE. Endosomal pH modulation by peptide-gold nanoparticle hybrids enables potent anti-inflammatory activity in phagocytic immune cells. Biomaterials. 2016;111:90\u2013102.","journal-title":"Biomaterials"},{"issue":"1","key":"803_CR18","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s12951-020-00593-7","volume":"18","author":"L Wang","year":"2020","unstructured":"Wang L, Zhang H, Sun L, Gao W, Xiong Y, Ma A, Liu X, Shen L, Li Q, Yang H. Manipulation of macrophage polarization by peptide-coated gold nanoparticles and its protective effects on acute lung injury. J Nanobiotechnology. 2020;18(1):38.","journal-title":"J Nanobiotechnology"},{"issue":"19","key":"803_CR19","doi-asserted-by":"publisher","first-page":"1800510","DOI":"10.1002\/adhm.201800510","volume":"7","author":"Y Xiong","year":"2018","unstructured":"Xiong Y, Gao W, Xia F, Sun Y, Sun L, Wang L, Ben S, Turvey SE, Yang H, Li Q. Peptide-gold nanoparticle hybrids as promising anti-inflammatory nanotherapeutics for acute lung injury: in vivo efficacy, biodistribution, and clearance. Adv Healthc Mater. 2018;7(19):1800510.","journal-title":"Adv Healthc Mater"},{"issue":"9","key":"803_CR20","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.1021\/ja972332i","volume":"120","author":"JJ Storhoff","year":"1998","unstructured":"Storhoff JJ, Elghanian R, Mucic RC, Mirkin CA, Letsinger RL. One-pot colorimetric differentiation of polynucleotides with single base imperfections using gold nanoparticle probes. J Am Chem Soc. 1998;120(9):1959\u201364.","journal-title":"J Am Chem Soc"},{"key":"803_CR21","doi-asserted-by":"publisher","DOI":"10.3791\/56689","author":"L Kozicky","year":"2017","unstructured":"Kozicky L, Sly LM. Assessment of antibody-based drugs effects on murine bone marrow and peritoneal macrophage activation. J Visualized Exp JoVE. 2017. https:\/\/doi.org\/10.3791\/56689.","journal-title":"J Visualized Exp JoVE"},{"issue":"5","key":"803_CR22","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1165\/rcmb.2009-0210ST","volume":"44","author":"G Matute-Bello","year":"2011","unstructured":"Matute-Bello G, Downey G, Moore BB, Groshong SD, Matthay MA, Slutsky AS, Kuebler WM. An official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals. Am J Respir Cell Mol Biol. 2011;44(5):725\u201338.","journal-title":"Am J Respir Cell Mol Biol"},{"key":"803_CR23","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.actbio.2018.12.046","volume":"85","author":"W Gao","year":"2019","unstructured":"Gao W, Wang Y, Xiong Y, Sun L, Wang L, Wang K, Lu HY, Bao A, Turvey SE, Li Q, Yang H. Size-dependent anti-inflammatory activity of a peptide-gold nanoparticle hybrid in vitro and in a mouse model of acute lung injury. Acta Biomater. 2019;85:203\u201317.","journal-title":"Acta Biomater"},{"issue":"2","key":"803_CR24","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1165\/rcmb.2012-0366MA","volume":"49","author":"R Zaynagetdinov","year":"2013","unstructured":"Zaynagetdinov R, Sherrill TP, Kendall PL, Segal BH, Weller KP, Tighe RM, Blackwell TS. Identification of myeloid cell subsets in murine lungs using flow cytometry. Am J Respir Cell Mol Biol. 2013;49(2):180\u20139.","journal-title":"Am J Respir Cell Mol Biol"},{"key":"803_CR25","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.jconrel.2019.04.005","volume":"303","author":"T Secher","year":"2019","unstructured":"Secher T, Dalonneau E, Ferreira M, Parent C, Azzopardi N, Paintaud G, Si-Tahar M, Heuze-Vourc\u2019h N. In a murine model of acute lung infection, airway administration of a therapeutic antibody confers greater protection than parenteral administration. J Control Release. 2019;303:24\u201333.","journal-title":"J Control Release"},{"issue":"6","key":"803_CR26","first-page":"583","volume":"4","author":"SY Gao","year":"2012","unstructured":"Gao SY, Huang JQ, Luo YF, Li ZP, Xie CM, Guo YB. Comparison of the lung function change in patients with COPD and bronchial asthma before and after treatment with budesonide\/formoterol. J Thorac Dis. 2012;4(6):583\u20137.","journal-title":"J Thorac Dis"},{"issue":"9","key":"803_CR27","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1164\/rccm.201505-1048OC","volume":"192","author":"DA Mahler","year":"2015","unstructured":"Mahler DA, Kerwin E, Ayers T, FowlerTaylor A, Maitra S, Thach C, Lloyd M, Patalano F, Banerji D. FLIGHT1 and FLIGHT2: efficacy and safety of QVA149 (indacaterol\/glycopyrrolate) versus its monocomponents and placebo in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2015;192(9):1068\u201379.","journal-title":"Am J Respir Crit Care Med."},{"issue":"25","key":"803_CR28","doi-asserted-by":"publisher","first-page":"6574","DOI":"10.1016\/j.biomaterials.2010.05.009","volume":"31","author":"J Lipka","year":"2010","unstructured":"Lipka J, Semmler-Behnke M, Sperling RA, Wenk A, Takenaka S, Schleh C, Kissel T, Parak WJ, Kreyling WG. Biodistribution of PEG-modified gold nanoparticles following intratracheal instillation and intravenous injection. Biomaterials. 2010;31(25):6574\u201381.","journal-title":"Biomaterials"},{"key":"803_CR29","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.jconrel.2016.01.020","volume":"240","author":"YN Zhang","year":"2016","unstructured":"Zhang YN, Poon W, Tavares AJ, McGilvray ID, Chan WCW. Nanoparticle-liver interactions: cellular uptake and hepatobiliary elimination. J Control Release. 2016;240:332\u201348.","journal-title":"J Control Release"},{"key":"803_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09893-5","author":"CS Umeshappa","year":"2019","unstructured":"Umeshappa CS, Singha S, Blanco J, Shao K, Nanjundappa RH, Yamanouchi J, Pares A, Serra P, Yang Y, Santamaria P. Suppression of a broad spectrum of liver autoimmune pathologies by single peptide-MHC-based nanomedicines. Nat Commun. 2019. https:\/\/doi.org\/10.1038\/s41467-019-09893-5.","journal-title":"Nat Commun"},{"issue":"4","key":"803_CR31","doi-asserted-by":"publisher","first-page":"4410","DOI":"10.1021\/acsnano.8b09655","volume":"13","author":"MB Violatto","year":"2019","unstructured":"Violatto MB, Casarin E, Talamini L, Russo L, Baldan S, Tondello C, Messmer M, Hintermann E, Rossi A, Passoni A, Bagnati R, Biffi S, Toffanin C, Gimondi S, Fumagalli S, De Simoni MG, Barisani D, Salmona M, Christen U, Invernizzi P, Bigini P, Morpurgo M. Dexamethasone conjugation to biodegradable avidin-nucleic-acid-nano-assemblies promotes selective liver targeting and improves therapeutic efficacy in an autoimmune hepatitis murine model. ACS Nano. 2019;13(4):4410\u201323.","journal-title":"ACS Nano"},{"issue":"7","key":"803_CR32","doi-asserted-by":"publisher","first-page":"3340","DOI":"10.7150\/thno.41239","volume":"10","author":"ZT Bennett","year":"2020","unstructured":"Bennett ZT, Feng Q, Bishop JA, Huang G, Sumer BD, Gao JM. Detection of lymph node metastases by ultra-pH-sensitive polymeric nanoparticles. Theranostics. 2020;10(7):3340\u201350.","journal-title":"Theranostics"}],"container-title":["Journal of Nanobiotechnology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12951-021-00803-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12951-021-00803-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12951-021-00803-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T11:13:21Z","timestamp":1614251601000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnanobiotechnology.biomedcentral.com\/articles\/10.1186\/s12951-021-00803-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,25]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["803"],"URL":"https:\/\/doi.org\/10.1186\/s12951-021-00803-w","relation":{},"ISSN":["1477-3155"],"issn-type":[{"value":"1477-3155","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,25]]},"assertion":[{"value":"17 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All animal protocols of this study were approved by the Research Animal Care and Use Committee of Shanghai General Hospital to Shanghai Jiao Tong University Medical School (Approval number: 2018KY201), which are in line with the American Association for Laboratory Animal Science (AALAS) guidelines.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All the authors consent for publication.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"56"}}