{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T14:09:01Z","timestamp":1780927741033,"version":"3.54.1"},"reference-count":49,"publisher":"Elsevier BV","issue":"20","license":[{"start":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T00:00:00Z","timestamp":1404172800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T00:00:00Z","timestamp":1404172800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81130059"],"award-info":[{"award-number":["81130059"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"crossref","award":["2009CB930300"],"award-info":[{"award-number":["2009CB930300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biomaterials"],"published-print":{"date-parts":[[2014,7]]},"DOI":"10.1016\/j.biomaterials.2014.03.036","type":"journal-article","created":{"date-parts":[[2014,4,13]],"date-time":"2014-04-13T14:15:17Z","timestamp":1397398517000},"page":"5347-5358","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":96,"title":["Combined mTOR inhibitor rapamycin and doxorubicin-loaded cyclic\u00a0octapeptide modified liposomes for targeting integrin \u03b13 in triple-negative breast cancer"],"prefix":"10.1016","volume":"35","author":[{"given":"Wenbing","family":"Dai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qihua","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.biomaterials.2014.03.036_bib1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1097\/GCO.0b013e32835c1633","article-title":"Updates in the treatment of basal\/triple-negative breast cancer","volume":"25","author":"Shastry","year":"2013","journal-title":"Curr Opin Obstet Gynecol"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.molonc.2010.04.006","article-title":"Triple-negative breast cancer: present challenges and new perspectives","volume":"4","author":"Podo","year":"2010","journal-title":"Mol Oncol"},{"issue":"Suppl.\u00a01","key":"10.1016\/j.biomaterials.2014.03.036_bib3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1634\/theoncologist.2011-S1-01","article-title":"Triple-negative breast cancer: an unmet medical need","volume":"16","author":"Hudis","year":"2011","journal-title":"Oncologist"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib4","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1177\/0897190012442062","article-title":"Triple negative breast cancer: a brief review of its characteristics and treatment options","volume":"25","author":"Griffiths","year":"2012","journal-title":"J\u00a0Pharm Pract"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib5","doi-asserted-by":"crossref","first-page":"2223","DOI":"10.1093\/annonc\/mds067","article-title":"Targeting triple-negative breast cancer: optimising therapeutic outcomes","volume":"23","author":"Gelmon","year":"2012","journal-title":"Ann Oncol"},{"issue":"Suppl.\u00a06","key":"10.1016\/j.biomaterials.2014.03.036_bib6","doi-asserted-by":"crossref","first-page":"vi13","DOI":"10.1093\/annonc\/mds188","article-title":"Understanding the biology of triple-negative breast cancer","volume":"23","author":"Criscitiello","year":"2012","journal-title":"Ann Oncol"},{"issue":"Suppl.\u00a06","key":"10.1016\/j.biomaterials.2014.03.036_bib7","doi-asserted-by":"crossref","first-page":"vi56","DOI":"10.1093\/annonc\/mds196","article-title":"Emerging targeted therapies in triple-negative breast cancer","volume":"23","author":"Crown","year":"2012","journal-title":"Ann Oncol"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib8","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.ctrv.2012.12.001","article-title":"Targeting triple negative breast cancer: Is p53 the answer?","volume":"39","author":"Turner","year":"2013","journal-title":"Cancer Treat Rev"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib9","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s10549-013-2421-5","article-title":"Molecularly targeted therapies for metastatic triple-negative breast cancer","volume":"138","author":"Bayraktar","year":"2013","journal-title":"Breast Cancer Res Treat"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib10","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1016\/S0002-9440(10)65227-3","article-title":"Immunohistochemical evidence of loss of PTEN expression in primary ductal adenocarcinomas of the breast","volume":"155","author":"Perren","year":"1999","journal-title":"Am J Pathol"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib11","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1158\/0008-5472-CAN-04-3913","article-title":"PIK3CA mutations correlate with hormone receptors, node metastasis, and ERBB2, and are mutually exclusive with PTEN loss in human breast carcinoma","volume":"65","author":"Saal","year":"2005","journal-title":"Cancer Res"},{"issue":"9","key":"10.1016\/j.biomaterials.2014.03.036_bib12","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1111\/j.1349-7006.2012.02359.x","article-title":"Efficacy of everolimus, a novel mTOR inhibitor, against basal-like triple-negative breast cancer cells","volume":"103","author":"Yunokawa","year":"2012","journal-title":"Cancer Sci"},{"issue":"3","key":"10.1016\/j.biomaterials.2014.03.036_bib13","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1158\/1078-0432.CCR-03-0043","article-title":"Determinants of rapamycin sensitivity in breast cancer cells","volume":"10","author":"Noh","year":"2004","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib14","first-page":"806","article-title":"Phosphorylated mTOR expression correlates with poor outcome in early-stage triple negative breast carcinomas","volume":"5","author":"Ueng","year":"2012","journal-title":"Int J Clin Exp Pathol"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib15","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.breast.2011.09.008","article-title":"mTOR in breast cancer: differential expression in triple-negative and non-triple-negative tumors","volume":"21","author":"Walsh","year":"2012","journal-title":"Breast"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib16","doi-asserted-by":"crossref","first-page":"3948","DOI":"10.4161\/cc.10.22.18124","article-title":"High-dose rapamycin induces apoptosis in human cancer cells by dissociating mTOR complex 1 and suppressing phosphorylation of 4E-BP1","volume":"10","author":"Yellen","year":"2011","journal-title":"Cell Cycle"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib17","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.bcp.2011.11.022","article-title":"Akt and p53 are potential mediators of reduced mammary tumor growth by chloroquine and the mTOR inhibitor RAD001","volume":"83","author":"Loehberg","year":"2012","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib18","doi-asserted-by":"crossref","first-page":"3937","DOI":"10.1038\/sj.onc.1206565","article-title":"Phospholipase D confers rapamycin resistance in human breast cancer cells","volume":"22","author":"Chen","year":"2003","journal-title":"Oncogene"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib19","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.canlet.2010.11.012","article-title":"Resveratrol enhances the anti-tumor activity of the mTOR inhibitor rapamycin in multiple breast cancer cell lines mainly by suppressing rapamycin-induced AKT signaling","volume":"301","author":"He","year":"2011","journal-title":"Cancer Lett"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib20","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.ejca.2010.01.014","article-title":"Treating triple-negative breast cancer by a combination of rapamycin and cyclophosphamide: an in\u00a0vivo bioluminescence imaging study","volume":"46","author":"Zeng","year":"2010","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib21","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.bcp.2007.04.003","article-title":"Cisplatin and doxorubicin repress vascular endothelial growth factor expression and differentially down-regulate hypoxia-inducible factor I activity in human ovarian cancer cells","volume":"74","author":"Duyndam","year":"2007","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib22","first-page":"2713","article-title":"The mTOR inhibitor RAD001 sensitizes tumor cells to the cytotoxic effect of carboplatin in breast cancer in\u00a0vitro","volume":"31","author":"Liu","year":"2011","journal-title":"Anticancer Res"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib23","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.1016\/j.ejca.2004.08.017","article-title":"Rapamycin inhibits doxorubicin-induced NF-\u03baB\/Rel nuclear activity and enhances the apoptosis of melanoma cells","volume":"40","author":"Romano","year":"2004","journal-title":"Eur J Cancer"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib24","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/j.yexcr.2006.12.004","article-title":"Confluence-dependent resistance to doxorubicin in human MDA-MB-231 breast carcinoma cells requires hypoxia-inducible factor-1 activity","volume":"313","author":"Fang","year":"2007","journal-title":"Exp Cell Res"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib25","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.bcp.2012.10.005","article-title":"Autophagy upregulation promotes survival and attenuates doxorubicin-induced cardiotoxicity","volume":"85","author":"Sishi","year":"2012","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib26","doi-asserted-by":"crossref","first-page":"6230","DOI":"10.1158\/0008-5472.CAN-12-1345","article-title":"Tumor cells upregulate normoxic HIF-1alpha in response to doxorubicin","volume":"73","author":"Cao","year":"2013","journal-title":"Cancer Res"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib27","doi-asserted-by":"crossref","first-page":"20534","DOI":"10.1074\/jbc.M611782200","article-title":"Hypoxia-inducible factor 1alpha is regulated by the mammalian target of rapamycin (mTOR) via an mTOR signaling motif","volume":"282","author":"Land","year":"2007","journal-title":"J\u00a0Biol Chem"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib28","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1007\/s10620-008-0605-3","article-title":"Antitumoral activity of rapamycin mediated through inhibition of HIF-1alpha and VEGF in hepatocellular carcinoma","volume":"54","author":"Wang","year":"2009","journal-title":"Dig Dis Sci"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib29","doi-asserted-by":"crossref","first-page":"6840","DOI":"10.1158\/1078-0432.CCR-11-0666","article-title":"A\u00a0phase I trial of liposomal doxorubicin, bevacizumab, and temsirolimus in patients with advanced gynecologic and breast malignancies","volume":"17","author":"Moroney","year":"2011","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib30","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1021\/jm801062d","article-title":"Discovery of targeting ligands for breast cancer cells using the one-bead one-compound combinatorial method","volume":"52","author":"Yao","year":"2009","journal-title":"J\u00a0Med Chem"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib31","doi-asserted-by":"crossref","first-page":"6744","DOI":"10.1021\/jm9012032","article-title":"Structure\u2013activity relationship studies of targeting ligands against breast cancer cells","volume":"52","author":"Yao","year":"2009","journal-title":"J\u00a0Med Chem"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib32","series-title":"d-Cys-d-Asp-Gly-Tyr(3-NO2)-Gly-ProOH-Asn-D-Cys-biotin-streptavidin-Cy5.5. Molecular imaging and contrast agent database (MICAD) [Internet]","author":"Leung","year":"2004-2013"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib33","doi-asserted-by":"crossref","first-page":"30","DOI":"10.7150\/thno\/v01p0030","article-title":"Why integrin as a primary target for imaging and therapy","volume":"1","author":"Niu","year":"2011","journal-title":"Theranostics"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib34","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.jconrel.2011.03.014","article-title":"Chloride channel-mediated brain glioma targeting of chlorotoxin-modified doxorubicine-loaded liposomes","volume":"152","author":"Xiang","year":"2011","journal-title":"J\u00a0Control Release"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib35","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/j.biomaterials.2012.10.034","article-title":"Rapamycin encapsulated in dual-responsive micelles for cancer therapy","volume":"34","author":"Chen","year":"2013","journal-title":"Biomaterials"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib36","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1016\/j.biomaterials.2012.12.012","article-title":"The reduction of tumor interstitial fluid pressure by liposomal imatinib and its effect on combination therapy with liposomal doxorubicin","volume":"34","author":"Fan","year":"2013","journal-title":"Biomaterials"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib37","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/0005-2736(93)90105-9","article-title":"Transmembrane ammonium sulfate gradient in liposomes produce efficient and stable entrapment of amphipathic weak bases","volume":"1151","author":"Haran","year":"1993","journal-title":"Biochim Biophys Acta"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib38","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/nprot.2006.179","article-title":"Sulforhodamine B colorimetric assay for cytotoxicity screening","volume":"1","author":"Vichai","year":"2006","journal-title":"Nat Protoc"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib39","doi-asserted-by":"crossref","first-page":"3878","DOI":"10.1158\/1535-7163.MCT-08-0476","article-title":"In\u00a0vivo characterization of a polymeric nanoparticle platform with potential oral drug delivery capabilities","volume":"7","author":"Bisht","year":"2008","journal-title":"Mol Cancer Ther"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib40","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1021\/mp200464x","article-title":"A\u00a0novel lanreotide-encoded micelle system targets paclitaxel to the tumors with overexpression of somatostatin receptors","volume":"9","author":"Zheng","year":"2012","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib41","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1006\/bbrc.1998.9389","article-title":"The role of \u03b12\u03b21 and \u03b13\u03b21 integrin receptors in the initial anchoring of MDA-MB-231 human breast cancer cells to cortical bone matrix","volume":"250","author":"Lundstrom","year":"1998","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib42","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1002\/1097-0215(20000801)87:3<336::AID-IJC5>3.0.CO;2-3","article-title":"The \u03b13\u03b21 integrin is associated with mammary carcinoma cell metastasis, invasion, and gelatinase B (MMP-9) activity","volume":"87","author":"Monica","year":"2000","journal-title":"Int J Cancer"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib43","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(99)00037-X","article-title":"Mechanisms and kinetics of liposome\u2013cell interactions","volume":"40","author":"D\u00fczg\u00fcne\u015f","year":"1999","journal-title":"Adv Drug Deliv Rev"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib44","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1124\/pr.58.3.10","article-title":"Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies","volume":"58","author":"Chou","year":"2006","journal-title":"Pharmacol Rev"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib45","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1158\/0008-5472.CAN-09-1947","article-title":"Drug combination studies and their synergy quantification using the Chou\u2013Talalay method","volume":"70","author":"Chou","year":"2010","journal-title":"Cancer Res"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib46","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.cis.2006.05.026","article-title":"Nanoparticles for bioimaging","volume":"123\u2013126","author":"Sharma","year":"2006","journal-title":"Adv Colloid Interface Sci"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib47","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1007\/s11095-011-0426-5","article-title":"How stealthy are PEG\u2013PLA nanoparticles? An NIR in\u00a0vivo study combined with detailed size measurements","volume":"28","author":"Sch\u00e4dlich","year":"2011","journal-title":"Pharm Res"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib48","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.jconrel.2012.07.010","article-title":"Analysis on the current status of targeted drug delivery to tumors","volume":"164","author":"Kwon","year":"2012","journal-title":"J\u00a0Control Release"},{"key":"10.1016\/j.biomaterials.2014.03.036_bib49","doi-asserted-by":"crossref","first-page":"657","DOI":"10.3892\/ol_00000115","article-title":"Role and mechanism of hypoxia-inducible factor-1 in cell growth and apoptosis of breast cancer cell line MDA-MB-231","volume":"1","author":"Shi","year":"2010","journal-title":"Oncol Lett"}],"container-title":["Biomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S014296121400283X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S014296121400283X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T15:59:10Z","timestamp":1758902350000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S014296121400283X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7]]},"references-count":49,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2014,7]]}},"alternative-id":["S014296121400283X"],"URL":"https:\/\/doi.org\/10.1016\/j.biomaterials.2014.03.036","relation":{},"ISSN":["0142-9612"],"issn-type":[{"value":"0142-9612","type":"print"}],"subject":[],"published":{"date-parts":[[2014,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Combined mTOR inhibitor rapamycin and doxorubicin-loaded cyclic\u00a0octapeptide modified liposomes for targeting integrin \u03b13 in triple-negative breast cancer","name":"articletitle","label":"Article Title"},{"value":"Biomaterials","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.biomaterials.2014.03.036","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2014 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}