{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T03:50:59Z","timestamp":1794282659154,"version":"4.9.0"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T00:00:00Z","timestamp":1655251200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T00:00:00Z","timestamp":1655251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82104106"],"award-info":[{"award-number":["82104106"]}],"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":["82073778"],"award-info":[{"award-number":["82073778"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["3332021044"],"award-info":[{"award-number":["3332021044"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2021-1-I2M-026"],"award-info":[{"award-number":["2021-1-I2M-026"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Nanobiotechnol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Oral chemotherapy is preferred for patients with cancer owing to its multiple advantages, including convenience, better patient compliance, and improved safety. Nevertheless, various physical barriers exist in this route that hamper the development of oral chemotherapeutic formulations, including destruction of drugs in the gastrointestinal tract (GIT), low permeability in enterocytes, and short residence time in the intestine. To overcome these limitations, it is necessary to design an efficient oral drug delivery system with high efficacy and improved safety.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Herein, we designed novel glycocholic acid (GCA)-functionalized double layer nanoparticles (GCA-NPs), which can act via an endogenous pathway and in a temporally controlled manner in the intestine, to enhance the oral bioavailability of hydrophobic chemotherapeutic drugs such as paclitaxel (PTX). GCA-NPs were composed of quercetin (Qu)-modified liposomes (QL) coated with GCA-chitosan oligosaccharide conjugate (GCOS). The GCA-NPs thus prepared showed prolonged intestinal retention time and good GIT stability due to the presence of chitosan oligosaccharide (COS) and enhanced active transportation via intestinal apical sodium-dependent bile acid transporter (ASBT) due to the presence of GCA. GCA-NPs also efficiently inhibited intestinal P-gp induced by Qu. PTX-loaded GCA-NPs (PTX@GCA-NPs) had a particle size of 84\u00a0nm and an entrapment efficiency of 98% with good stability. As a result, the oral bioavailability of PTX was increased 19-fold compared to that of oral Taxol<jats:sup>\u00ae<\/jats:sup> at the same dose. Oral PTX@GCA-NPs displayed superior antitumor efficacy and better safety than Taxol<jats:sup>\u00ae<\/jats:sup> when administered intravenously.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our novel drug delivery system showed remarkable efficacy in overcoming multiple limitations and is a promising carrier for oral delivery of multiple drugs, which addresses several challenges in oral delivery in the clinical context.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1186\/s12951-022-01460-3","type":"journal-article","created":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T10:02:53Z","timestamp":1655287373000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Biomimetic and temporal-controlled nanocarriers with ileum transporter targeting for achieving oral administration of chemotherapeutic drugs"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1129-0595","authenticated-orcid":false,"given":"Wei","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Xin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xintong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingji","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingzhe","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonggao","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,15]]},"reference":[{"issue":"1","key":"1460_CR1","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.jconrel.2013.04.020","volume":"170","author":"K Thanki","year":"2013","unstructured":"Thanki K, Gangwal RP, Sangamwar AT, Jain S. Oral delivery of anticancer drugs: challenges and opportunities. J Control Release. 2013;170(1):15\u201340.","journal-title":"J Control Release"},{"issue":"9","key":"1460_CR2","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1038\/sj.bjc.6600591","volume":"87","author":"VJ O'Neill","year":"2002","unstructured":"O\u2019Neill VJ, Twelves CJ. Oral cancer treatment: developments in chemotherapy and beyond. Br J Cancer. 2002;87(9):933\u20137.","journal-title":"Br J Cancer"},{"issue":"9","key":"1460_CR3","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1093\/jnci\/94.9.652","volume":"94","author":"HG Ann","year":"2002","unstructured":"Ann HG, Jerry A, Philip SW, Eric PW. Adherence to therapy with oral antineoplastic agents. J Natl Cancer Inst. 2002;94(9):652\u201361.","journal-title":"J Natl Cancer Inst"},{"issue":"8","key":"1460_CR4","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/j.ctrv.2010.04.005","volume":"36","author":"GL Banna","year":"2010","unstructured":"Banna GL, Collova E, Gebbia V, Lipari H, Giuffrida P, Cavallaro S, Condorelli R, Buscarino C, Tralongo P, Ferrau F. Anticancer oral therapy: emerging related issues. Cancer Treat Rev. 2010;36(8):595\u2013605.","journal-title":"Cancer Treat Rev"},{"key":"1460_CR5","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.jconrel.2016.06.016","volume":"240","author":"AA Date","year":"2016","unstructured":"Date AA, Hanes J, Ensign LM. Nanoparticles for oral delivery: design, evaluation and state-of-the-art. J Contol Release. 2016;240:504\u201326.","journal-title":"J Contol Release"},{"issue":"Pt B","key":"1460_CR6","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.addr.2016.07.007","volume":"106","author":"P Lundquist","year":"2016","unstructured":"Lundquist P, Artursson P. Oral absorption of peptides and nanoparticles across the human intestine: opportunities, limitations and studies in human tissues. Adv Drug Deliv Rev. 2016;106(Pt B):256\u201376.","journal-title":"Adv Drug Deliv Rev"},{"key":"1460_CR7","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.618411","volume":"12","author":"MS Alqahtani","year":"2021","unstructured":"Alqahtani MS, Kazi M, Alsenaidy MA, Ahmad MZ. Advances in {O\u2019Neill, 2002 #24}{Madni, 2020 #36}{Park, 2017 #39}{Manconi, 2017 #46}Oral Drug Delivery. Front Pharmacol. 2021;12: 618411.","journal-title":"Front Pharmacol"},{"issue":"2","key":"1460_CR8","doi-asserted-by":"publisher","first-page":"287","DOI":"10.2217\/nnm.09.110","volume":"5","author":"R Emilie","year":"2010","unstructured":"Emilie R, Frederic L, Emmanuel G, Jean PB. Biopharmaceutical parameters to consider in order to alter the fate of nanocarriers after oral delivery. Nanomedicine (Lond). 2010;5(2):287\u2013306.","journal-title":"Nanomedicine (Lond)"},{"issue":"4","key":"1460_CR9","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1007\/s42765-020-00040-0","volume":"2","author":"C Chen","year":"2020","unstructured":"Chen C, Wu Z, Ding P, Sun N, Liu H, Chen Y, Wang Z, Pei R. Peptide NGR modified TiO2 nanofiber substrate for circulating tumor cells capture. Adv Fiber Mater. 2020;2(4):186\u201393.","journal-title":"Adv Fiber Mater"},{"issue":"5","key":"1460_CR10","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/s42765-020-00053-9","volume":"2","author":"J Zhao","year":"2020","unstructured":"Zhao J, Cui W. Functional electrospun fibers for local therapy of cancer. Adv Fiber Mater. 2020;2(5):229\u201345.","journal-title":"Adv Fiber Mater"},{"issue":"3","key":"1460_CR11","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1007\/s42765-021-00075-x","volume":"3","author":"M Wang","year":"2021","unstructured":"Wang M, Tan Y, Li D, Xu G, Yin D, Xiao Y, Xu T, Chen X, Zhu X, Shi X. Negative isolation of circulating tumor cells using a microfluidic platform integrated with streptavidin-functionalized PLGA nanofibers. Adv Fiber Mater. 2021;3(3):192\u2013202.","journal-title":"Adv Fiber Mater"},{"issue":"4","key":"1460_CR12","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1039\/C9BM01378D","volume":"8","author":"X Hu","year":"2020","unstructured":"Hu X, Yang G, Chen S, Luo S, Zhang J. Biomimetic and bioinspired strategies for oral drug delivery. Biomater Si. 2020;8(4):1020\u201344.","journal-title":"Biomater Si"},{"key":"1460_CR13","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.jconrel.2020.07.034","volume":"327","author":"F Deng","year":"2020","unstructured":"Deng F, Bae YH. Bile acid transporter-mediated oral drug delivery. J Contol Release. 2020;327:100\u201316.","journal-title":"J Contol Release"},{"issue":"1","key":"1460_CR14","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1208\/s12249-020-01873-z","volume":"22","author":"A Madni","year":"2020","unstructured":"Madni A, Rehman S, Sultan H, Khan MM, Ahmad F, Raza MR, Rai N, Parveen F. Mechanistic approaches of internalization, subcellular trafficking, and cytotoxicity of nanoparticles for targeting the small intestine. AAPS PharmSciTech. 2020;22(1):3.","journal-title":"AAPS PharmSciTech"},{"key":"1460_CR15","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107539","volume":"212","author":"M Li","year":"2020","unstructured":"Li M, Wang Q, Li Y, Cao S, Zhang Y, Wang Z, Liu G, Li J, Gu B. Apical sodium-dependent bile acid transporter, drug target for bile acid related diseases and delivery target for prodrugs: current and future challenges. Pharmacol Ther. 2020;212: 107539.","journal-title":"Pharmacol Ther"},{"issue":"10","key":"1460_CR16","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1007\/s11095-007-9289-1","volume":"24","author":"WA Alrefai","year":"2007","unstructured":"Alrefai WA, Gill RK. Bile acid transporters: structure, function, regulation and pathophysiological implications. Pharm Res. 2007;24(10):1803\u201323.","journal-title":"Pharm Res"},{"key":"1460_CR17","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.biomaterials.2017.09.022","volume":"147","author":"J Park","year":"2017","unstructured":"Park J, Choi JU, Kim K, Byun Y. Bile acid transporter mediated endocytosis of oral bile acid conjugated nanocomplex. Biomaterials. 2017;147:145\u201354.","journal-title":"Biomaterials"},{"issue":"9","key":"1460_CR18","doi-asserted-by":"publisher","first-page":"8893","DOI":"10.1021\/acsnano.8b04315","volume":"12","author":"KS Kim","year":"2018","unstructured":"Kim KS, Suzuki K, Cho H, Youn YS, Bae YH. Oral nanoparticles exhibit specific high-efficiency intestinal uptake and lymphatic transport. ACS Nano. 2018;12(9):8893\u2013900.","journal-title":"ACS Nano"},{"key":"1460_CR19","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110835","volume":"132","author":"N Yang","year":"2020","unstructured":"Yang N, Dong YQ, Jia GX, Fan SM, Li SZ, Yang SS, Li YB. ASBT(SLC10A2): a promising target for treatment of diseases and drug discovery. Biomed Pharmacother. 2020;132: 110835.","journal-title":"Biomed Pharmacother"},{"key":"1460_CR20","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.biomaterials.2017.10.022","volume":"151","author":"W Fan","year":"2018","unstructured":"Fan W, Xia D, Zhu Q, Li X, He S, Zhu C, Guo S, Hovgaard L, Yang M, Gan Y. Functional nanoparticles exploit the bile acid pathway to overcome multiple barriers of the intestinal epithelium for oral insulin delivery. Biomaterials. 2018;151:13\u201323.","journal-title":"Biomaterials"},{"key":"1460_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.120944","volume":"275","author":"Y Han","year":"2021","unstructured":"Han Y, Liu W, Chen L, Xin X, Wang Q, Zhang X, Jin M, Gao Z, Huang W. Effective oral delivery of Exenatide-Zn(2+) complex through distal ileum-targeted double layers nanocarriers modified with deoxycholic acid and glycocholic acid in diabetes therapy. Biomaterials. 2021;275: 120944.","journal-title":"Biomaterials"},{"issue":"1","key":"1460_CR22","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.ijpharm.2017.04.044","volume":"525","author":"M Manconi","year":"2017","unstructured":"Manconi M, Manca ML, Valenti D, Escribano E, Hillaireau H, Fadda AM, Fattal E. Chitosan and hyaluronan coated liposomes for pulmonary administration of curcumin. Int J Pharm. 2017;525(1):203\u201310.","journal-title":"Int J Pharm"},{"key":"1460_CR23","first-page":"325","volume":"11","author":"WL Chen","year":"2016","unstructured":"Chen WL, Yuan ZQ, Liu Y, Yang SD, Zhang CG, Li JZ, Zhu WJ, Li F, Zhou XF, Lin YM, et al. Liposomes coated with N-trimethyl chitosan to improve the absorption of harmine in vivo and in vitro. Int J Nanomedicine. 2016;11:325\u201336.","journal-title":"Int J Nanomedicine"},{"issue":"1","key":"1460_CR24","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1179\/joc.2005.17.1.86","volume":"17","author":"P Limtrakul","year":"2005","unstructured":"Limtrakul P, Khantamat O, Pintha K. Inhibition of P-glycoprotein function and expression by kaempferol and quercetin. J Chemother. 2005;17(1):86\u201395.","journal-title":"J Chemother"},{"key":"1460_CR25","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.carbpol.2018.09.020","volume":"203","author":"Y Mu","year":"2019","unstructured":"Mu Y, Fu Y, Li J, Yu X, Li Y, Wang Y, Wu X, Zhang K, Kong M, Feng C, et al. Multifunctional quercetin conjugated chitosan nano-micelles with P-gp inhibition and permeation enhancement of anticancer drug. Carbohydr Polym. 2019;203:10\u20138.","journal-title":"Carbohydr Polym"},{"issue":"26","key":"1460_CR26","doi-asserted-by":"publisher","first-page":"7654","DOI":"10.1016\/j.biomaterials.2014.05.053","volume":"35","author":"X Wang","year":"2014","unstructured":"Wang X, Chen Y, Dahmani FZ, Yin L, Zhou J, Yao J. Amphiphilic carboxymethyl chitosan-quercetin conjugate with P-gp inhibitory properties for oral delivery of paclitaxel. Biomaterials. 2014;35(26):7654\u201365.","journal-title":"Biomaterials"},{"issue":"3","key":"1460_CR27","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209\u201349.","journal-title":"CA Cancer J Clin"},{"issue":"7689","key":"1460_CR28","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1038\/nature25183","volume":"553","author":"RS Herbst","year":"2018","unstructured":"Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature. 2018;553(7689):446\u201354.","journal-title":"Nature"},{"key":"1460_CR29","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.jconrel.2021.07.014","volume":"337","author":"S Ghosh","year":"2021","unstructured":"Ghosh S, Javia A, Shetty S, Bardoliwala D, Maiti K, Banerjee S, Khopade A, Misra A, Sawant K, Bhowmick S. Triple negative breast cancer and non-small cell lung cancer: Clinical challenges and nano-formulation approaches. J Contol Release. 2021;337:27\u201358.","journal-title":"J Contol Release"},{"key":"1460_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.120790","volume":"272","author":"Y Zhang","year":"2021","unstructured":"Zhang Y, Zhang W, Wang Y, Zhu J, Zhou M, Peng C, He Z, Sun J, Li Z, Gui S. Emerging nanotaxanes for cancer therapy. Biomaterials. 2021;272: 120790.","journal-title":"Biomaterials"},{"issue":"6","key":"1460_CR31","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1016\/j.addr.2012.11.005","volume":"65","author":"L Mei","year":"2013","unstructured":"Mei L, Zhang Z, Zhao L, Huang L, Yang XL, Tang J, Feng SS. Pharmaceutical nanotechnology for oral delivery of anticancer drugs. Adv Drug Deliv Rev. 2013;65(6):880\u201390.","journal-title":"Adv Drug Deliv Rev"},{"issue":"49","key":"1460_CR32","doi-asserted-by":"publisher","first-page":"42186","DOI":"10.1021\/acsami.8b18979","volume":"10","author":"Z Le","year":"2018","unstructured":"Le Z, Chen Y, Han H, Tian H, Zhao P, Yang C, He Z, Liu L, Leong KW, Mao HQ, et al. Hydrogen-bonded tannic acid-based anticancer nanoparticle for enhancement of oral chemotherapy. ACS Appl Mater Interfaces. 2018;10(49):42186\u201397.","journal-title":"ACS Appl Mater Interfaces"},{"key":"1460_CR33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2021.120496","volume":"600","author":"X Lu","year":"2021","unstructured":"Lu X, Wu H, Liang Y, Zhang Z, Lv H. Redox-responsive prodrug for improving oral bioavailability of paclitaxel through bile acid transporter-mediated pathway. Int J Pharm. 2021;600: 120496.","journal-title":"Int J Pharm"},{"key":"1460_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2021.105713","volume":"159","author":"W Yao","year":"2021","unstructured":"Yao W, Xu Z, Sun J, Luo J, Wei Y, Zou J. Deoxycholic acid-functionalised nanoparticles for oral delivery of rhein. Eur J Pharm Sci. 2021;159: 105713.","journal-title":"Eur J Pharm Sci"},{"issue":"1","key":"1460_CR35","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1080\/10717544.2019.1710623","volume":"27","author":"L Kou","year":"2020","unstructured":"Kou L, Sun R, Xiao S, Cui X, Sun J, Ganapathy V, Yao Q, Chen R. OCTN2-targeted nanoparticles for oral delivery of paclitaxel: differential impact of the polyethylene glycol linker size on drug delivery in vitro, in situ, and in vivo. Drug deliv. 2020;27(1):170\u20139.","journal-title":"Drug deliv"},{"key":"1460_CR36","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.2147\/IJN.S195375","volume":"14","author":"M Wang","year":"2019","unstructured":"Wang M, Chen L, Huang W, Jin M, Wang Q, Gao Z, Jin Z. Improving the anti-keloid outcomes through liposomes loading paclitaxel-cholesterol complexes. Int J Nanomedicine. 2019;14:1385\u2013400.","journal-title":"Int J Nanomedicine"},{"issue":"6","key":"1460_CR37","first-page":"765","volume":"54","author":"G Debora","year":"2002","unstructured":"Debora G, Cristiane C, Silvana T, Renato B, Raul C. Use of a cholesterol-rich emulsion that binds to low-density lipoprotein receptors as a vehicle for paclitaxel. J Pharm Pharmacol. 2002;54(6):765\u201372.","journal-title":"J Pharm Pharmacol"},{"key":"1460_CR38","doi-asserted-by":"publisher","first-page":"689","DOI":"10.2147\/IJN.S188667","volume":"14","author":"XY Chu","year":"2019","unstructured":"Chu XY, Huang W, Wang YL, Meng LW, Chen LQ, Jin MJ, Chen L, Gao CH, Ge C, Gao ZG, et al. Improving antitumor outcomes for palliative intratumoral injection therapy through lecithin- chitosan nanoparticles loading paclitaxel- cholesterol complex. Int J Nanomedicine. 2019;14:689\u2013705.","journal-title":"Int J Nanomedicine"},{"key":"1460_CR39","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.jconrel.2013.12.034","volume":"177","author":"Z Khatun","year":"2014","unstructured":"Khatun Z, Nurunnabi M, Cho KJ, Byun Y, Bae YH, Lee YK. Oral absorption mechanism and anti-angiogenesis effect of taurocholic acid-linked heparin-docetaxel conjugates. J Contol Release. 2014;177:64\u201373.","journal-title":"J Contol Release."},{"issue":"5","key":"1460_CR40","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1016\/j.drudis.2016.04.007","volume":"21","author":"W Fan","year":"2016","unstructured":"Fan W, Xia D, Zhu Q, Hu L, Gan Y. Intracellular transport of nanocarriers across the intestinal epithelium. Drug Discov Today. 2016;21(5):856\u201363.","journal-title":"Drug Discov Today"},{"issue":"40","key":"1460_CR41","doi-asserted-by":"publisher","first-page":"34039","DOI":"10.1021\/acsami.8b13707","volume":"10","author":"Y Zheng","year":"2018","unstructured":"Zheng Y, Wu J, Shan W, Wu L, Zhou R, Liu M, Cui Y, Zhou M, Zhang Z, Huang Y. Multifunctional nanoparticles enable efficient oral delivery of biomacromolecules via improving payload stability and regulating the transcytosis pathway. ACS Appl Mater Interfaces. 2018;10(40):34039\u201349.","journal-title":"ACS Appl Mater Interfaces"},{"issue":"4","key":"1460_CR42","doi-asserted-by":"publisher","first-page":"2590","DOI":"10.1002\/med.21797","volume":"41","author":"Z Zhang","year":"2021","unstructured":"Zhang Z, Qi J, Lu Y, Wu W, Yuan H. Peroral targeting of drug micro or nanocarriers to sites beyond the gastrointestinal tract. Med Res Rev. 2021;41(4):2590\u20138.","journal-title":"Med Res Rev"},{"issue":"7","key":"1460_CR43","doi-asserted-by":"publisher","first-page":"5803","DOI":"10.1021\/acsami.6b15151","volume":"9","author":"F Deng","year":"2017","unstructured":"Deng F, Zhang H, Wang X, Zhang Y, Hu H, Song S, Dai W, He B, Zheng Y, Wang X, et al. Transmembrane pathways and mechanisms of rod-like paclitaxel nanocrystals through MDCK polarized monolayer. ACS Appl Mater Interfaces. 2017;9(7):5803\u201316.","journal-title":"ACS Appl Mater Interfaces"},{"issue":"8","key":"1460_CR44","doi-asserted-by":"publisher","first-page":"2449","DOI":"10.1016\/j.apsb.2020.12.022","volume":"11","author":"Z Zhang","year":"2021","unstructured":"Zhang Z, Lu Y, Qi J, Wu W. An update on oral drug delivery via intestinal lymphatic transport. Acta Pharm Sin B. 2021;11(8):2449\u201368.","journal-title":"Acta Pharm Sin B"},{"key":"1460_CR45","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.canlet.2016.12.018","volume":"400","author":"E Biziota","year":"2017","unstructured":"Biziota E, Mavroeidis L, Hatzimichael E, Pappas P. Metronomic chemotherapy: a potent macerator of cancer by inducing angiogenesis suppression and antitumor immune activation. Cancer Lett. 2017;400:243\u201351.","journal-title":"Cancer Lett"},{"key":"1460_CR46","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.canlet.2017.01.040","volume":"400","author":"YL Chen","year":"2017","unstructured":"Chen YL, Chang MC, Cheng WF. Metronomic chemotherapy and immunotherapy in cancer treatment. Cancer Lett. 2017;400:282\u201392.","journal-title":"Cancer Lett"},{"key":"1460_CR47","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.jconrel.2019.08.027","volume":"311\u2013312","author":"KS Kim","year":"2019","unstructured":"Kim KS, Youn YS, Bae YH. Immune-triggered cancer treatment by intestinal lymphatic delivery of docetaxel-loaded nanoparticle. J Contol Release. 2019;311\u2013312:85\u201395.","journal-title":"J Contol Release"},{"key":"1460_CR48","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.yrtph.2017.10.023","volume":"91","author":"H Choudhury","year":"2017","unstructured":"Choudhury H, Gorain B, Tekade RK, Pandey M, Karmakar S, Pal TK. Safety against nephrotoxicity in paclitaxel treatment: Oral nanocarrier as an effective tool in preclinical evaluation with marked in vivo antitumor activity. Regul Toxicol Pharmacol. 2017;91:179\u201389.","journal-title":"Regul Toxicol Pharmacol"},{"issue":"1","key":"1460_CR49","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1080\/08982104.2018.1458863","volume":"29","author":"X Fu","year":"2019","unstructured":"Fu X, Lu Y, Guo J, Liu H, Deng A, Kuang C, Xie X. K237-modified thermosensitive liposome enhanced the delivery efficiency and cytotoxicity of paclitaxel in vitro. J Liposome Res. 2019;29(1):86\u201393.","journal-title":"J Liposome Res"},{"issue":"18","key":"1460_CR50","doi-asserted-by":"publisher","first-page":"9691","DOI":"10.1021\/acsami.5b01473","volume":"7","author":"L Zhang","year":"2015","unstructured":"Zhang L, Wang Y, Yang Y, Liu Y, Ruan S, Zhang Q, Tai X, Chen J, Xia T, Qiu Y, et al. High tumor penetration of paclitaxel loaded pH sensitive cleavable liposomes by depletion of tumor collagen I in breast cancer. ACS Appl Mater Interfaces. 2015;7(18):9691\u2013701.","journal-title":"ACS Appl Mater Interfaces"},{"key":"1460_CR51","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/j.jconrel.2020.02.034","volume":"321","author":"H Cheng","year":"2020","unstructured":"Cheng H, Zhang X, Qin L, Huo Y, Cui Z, Liu C, Sun Y, Guan J, Mao S. Design of self-polymerized insulin loaded poly(n-butylcyanoacrylate) nanoparticles for tunable oral delivery. J Control Release. 2020;321:641\u201353.","journal-title":"J Control Release"},{"key":"1460_CR52","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.2147\/IJN.S125047","volume":"12","author":"Y Li","year":"2017","unstructured":"Li Y, Zhu C. Mechanism of hepatic targeting via oral administration of DSPE-PEG-cholic acid-modified nanoliposomes. Int J Nanomedicine. 2017;12:1673\u201384.","journal-title":"Int J Nanomedicine"}],"updated-by":[{"DOI":"10.1186\/s12951-022-01744-8","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T00:00:00Z","timestamp":1672099200000}}],"container-title":["Journal of Nanobiotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12951-022-01460-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12951-022-01460-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12951-022-01460-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T08:06:29Z","timestamp":1672128389000},"score":1,"resource":{"primary":{"URL":"https:\/\/jnanobiotechnology.biomedcentral.com\/articles\/10.1186\/s12951-022-01460-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,15]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["1460"],"URL":"https:\/\/doi.org\/10.1186\/s12951-022-01460-3","relation":{"correction":[{"id-type":"doi","id":"10.1186\/s12951-022-01744-8","asserted-by":"object"}]},"ISSN":["1477-3155"],"issn-type":[{"value":"1477-3155","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,15]]},"assertion":[{"value":"5 January 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 May 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 June 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 December 2022","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1186\/s12951-022-01744-8","URL":"https:\/\/doi.org\/10.1186\/s12951-022-01744-8","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"281"}}