{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:47:59Z","timestamp":1792788479593,"version":"4.5.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T00:00:00Z","timestamp":1609891200000},"content-version":"vor","delay-in-days":5,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Nutrition 2000Plus Foundation"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["AAPS PharmSciTech"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    It has been shown that long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) could act synergistically with 5-fluorouracil (5-FU) to kill cancer cells. To facilitate their simultaneous transport in the bloodstream, we synthesized, for the first time, liposomes (LIPUFU) containing 5-FU in the aqueous core and docosahexaenoic acid (DHA)\/eicosapentaenoic acid (EPA) at a ratio of 1:2 in the lipid bilayer. LIPUFU werestable with uniform size of 154 \u00b1 4 nm, PDI of 0.19 \u00b1 0.03 and zeta potential of -41 \u00b1 2 mV.\u00a0They contained 557\u2009\u00b1\u2009210\u00a0\u03bcmol\/l DHA, 1467\u2009\u00b1\u2009362\u00a0\u03bcmol\/l EPA, and 9.8\u2009\u00b1\u20091.1\u00a0\u03bcmol\/l 5-FU. Control liposomes without (LIP) or with only 5-FU (LIFU) or n-3 PUFAs (LIPU) were produced in a similar way. The effects of these different liposomal formulations on the cell cycle, growth, and apoptosis were evaluated in two human colorectal cancer (CRC) cell lines differing in sensitivity to 5-FU, using fluorescence-activated cell sorting analyses. LIPUFU were more cytotoxic than LIP, LIFU, and LIPU in both LS174T (p53\n                    <jats:sup>+\/+<\/jats:sup>\n                    , bax\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) and HT-29 (p53\n                    <jats:sup>\u2212\/0<\/jats:sup>\n                    , bax\n                    <jats:sup>+\/+<\/jats:sup>\n                    ) cell lines. Similar to LIFU, LIPUFU increased the percentage of cells in S phase, apoptosis, and\/or necrosis. The cytotoxic potential of LIPUFU was confirmed\n                    <jats:italic>in vivo<\/jats:italic>\n                    by tumor growth inhibition in the chicken chorioallantoic membrane model. These results suggest that LIPUFU could be considered to facilitate the simultaneous transport of 5-FU and n-3 PUFAs to the tumor site, in particular in case of CRC liver metastases.\n                  <\/jats:p>","DOI":"10.1208\/s12249-020-01897-5","type":"journal-article","created":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T11:10:51Z","timestamp":1609931451000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Antitumor Effect of 5-Fluorouracil-Loaded Liposomes Containing n-3 Polyunsaturated Fatty Acids in Two Different Colorectal Cancer Cell Lines"],"prefix":"10.1208","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4891-0487","authenticated-orcid":false,"given":"Yves Marc","family":"Dupertuis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Boulens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Angibaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Sophia","family":"Briod","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Viglione","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"All\u00e9mann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Delie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Pichard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,6]]},"reference":[{"key":"1897_CR1","doi-asserted-by":"publisher","unstructured":"Keum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. Springer Science and Business Media LLC. 2019;16(12):713\u2013732. https:\/\/doi.org\/10.1038\/s41575-019-0189-8.","DOI":"10.1038\/s41575-019-0189-8"},{"key":"1897_CR2","doi-asserted-by":"crossref","unstructured":"Rougier P, Mitry E. Epidemiology, treatment and chemoprevention in colorectal cancer. Ann Oncol Off J Eur Soc Med Oncol. 2003 [cited 2019 Oct 14];14 Suppl 2:ii3\u20135. Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/12810450.","DOI":"10.1093\/annonc\/mdg722"},{"key":"1897_CR3","doi-asserted-by":"crossref","unstructured":"Cunningham D, Atkin W, Lenz H-J, Lynch HT, Minsky B, Nordlinger B, et al. Colorectal cancer. Lancet. 2010 [cited 2019 Oct 14];375:1030\u201347. Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20304247.","DOI":"10.1016\/S0140-6736(10)60353-4"},{"key":"1897_CR4","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1093\/annonc\/mdh264","volume":"15","author":"P Noordhuis","year":"2004","unstructured":"Noordhuis P, Holwerda U, Van der Wilt CL, Van Groeningen CJ, Smid K, Meijer S, et al. 5-Fluorouracil incorporation into RNA and DNA in relation to thymidylate synthase inhibition of human colorectal cancers. Ann Oncol. 2004;15:1025\u201332.","journal-title":"Ann Oncol"},{"issue":"1","key":"1897_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.clcc.2014.11.002","volume":"14","author":"B Gustavsson","year":"2015","unstructured":"Gustavsson B, Carlsson G, MacHover D, Petrelli N, Roth A, Schmoll HJ, et al. A review of the evolution of systemic chemotherapy in the management of colorectal cancer. Clin Colorectal Cancer. 2015;14(1):1\u201310. https:\/\/doi.org\/10.1016\/j.clcc.2014.11.002.","journal-title":"Clin Colorectal Cancer."},{"key":"1897_CR6","first-page":"2203","volume":"47","author":"GD Heggie","year":"1987","unstructured":"Heggie GD, Sommadossi JP, Cross DS, Huster WJ. Clinical pharmacokinetics of 5-fluorouracil and its metabolites in plasma, urine, and bile. Cancer Res. 1987;47:2203\u20136.","journal-title":"Cancer Res"},{"key":"1897_CR7","doi-asserted-by":"publisher","unstructured":"Goirand F, Lemaitre F, Launay M, Tron C, Chatelut E, Boyer JC, et al. How can we best monitor 5-FU administration to maximize benefit to risk ratio? Expert Opin Drug Metab Toxicol. Taylor & Francis; 2018;14:1303\u201313. Available from: https:\/\/doi.org\/10.1080\/17425255.2018.1550484.","DOI":"10.1080\/17425255.2018.1550484"},{"key":"1897_CR8","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.jconrel.2015.01.021","volume":"208","author":"S Mura","year":"2015","unstructured":"Mura S, Bui DT, Couvreur P, Nicolas J. Lipid prodrug nanocarriers in cancer therapy. J Control Release Elsevier. 2015;208:25\u201341.","journal-title":"J Control Release"},{"key":"1897_CR9","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.ejps.2017.12.011","volume":"114","author":"E Moghimipour","year":"2018","unstructured":"Moghimipour E, Rezaei M, Ramezani Z, Kouchak M, Amini M, Angali KA, et al. Folic acid-modified liposomal drug delivery strategy for tumor targeting of 5-fluorouracil. Eur J Pharm Sci. Elsevier B.V. 2018;114:166\u201374.","journal-title":"Eur J Pharm Sci"},{"key":"1897_CR10","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1016\/j.biopha.2018.09.128","volume":"108","author":"S Handali","year":"2018","unstructured":"Handali S, Moghimipour E, Rezaei M, Ramezani Z, Kouchak M, Amini M, et al. A novel 5-fluorouracil targeted delivery to colon cancer using folic acid conjugated liposomes. Biomed Pharmacother Elsevier Masson SAS. 2018;108:1259\u201373.","journal-title":"Biomed Pharmacother"},{"key":"1897_CR11","doi-asserted-by":"publisher","unstructured":"Handali S, Moghimipour E, Kouchak M, Ramezani Z, Amini M, Angali KA, et al. New folate receptor targeted nano liposomes for delivery of 5-fluorouracil to cancer cells: strong implication for enhanced potency and safety. Life Sci. Elsevier; 2019;227:39\u201350. Available from: https:\/\/doi.org\/10.1016\/j.lfs.2019.04.030.","DOI":"10.1016\/j.lfs.2019.04.030"},{"key":"1897_CR12","doi-asserted-by":"publisher","first-page":"15008","DOI":"10.1088\/2043-6254\/aa5982","volume":"8","author":"A Tsend-Ayush","year":"2017","unstructured":"Tsend-Ayush A, Zhu X, Ding Y. Enhanced anticancer efficacy and tumor targeting through folate-PEG modified nanoliposome loaded with 5-fluorouracil related content lactobionic acid-conjugated TPGS nanoparticles for enhancing therapeutic efficacy of etoposide against hepatocellular carcinoma. Adv Nat Sci Nanosci Nanotechnol. 2017;8:15008.","journal-title":"Adv Nat Sci Nanosci Nanotechnol"},{"key":"1897_CR13","doi-asserted-by":"publisher","unstructured":"Tiwari A, Saraf S, Jain A, Panda PK, Verma A, Jain SK. Basics to advances in nanotherapy of colorectal cancer. Drug Deliv Transl Res. 2020 [cited 2020 Apr 16]:319\u201338. Available from: https:\/\/doi.org\/10.1007\/s13346-019-00680-9.","DOI":"10.1007\/s13346-019-00680-9"},{"key":"1897_CR14","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1097\/MCO.0b013e3281e2c9d4","volume":"10","author":"YM Dupertuis","year":"2007","unstructured":"Dupertuis YM, Meguid MM, Pichard C. Colon cancer therapy: new perspectives of nutritional manipulations using polyunsaturated fatty acids. Curr Opin Clin Nutr Metab Care. 2007;10:427\u201332.","journal-title":"Curr Opin Clin Nutr Metab Care"},{"key":"1897_CR15","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1007\/s10555-018-9744-y","volume":"37","author":"M Volpato","year":"2018","unstructured":"Volpato M, Hull MA. Omega-3 polyunsaturated fatty acids as adjuvant therapy of colorectal cancer. Cancer Metastasis Rev. 2018;37:545\u201355.","journal-title":"Cancer Metastasis Rev"},{"key":"1897_CR16","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1017\/S000711451200308X","volume":"109","author":"V Granci","year":"2013","unstructured":"Granci V, Cai F, Lecumberri E, Clerc A, Dupertuis YM, Pichard C. Colon cancer cell chemosensitisation by fish oil emulsion involves apoptotic mitochondria pathway. Br J Nutr. 2013;109:1188\u201395.","journal-title":"Br J Nutr"},{"key":"1897_CR17","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1007\/s00280-014-2497-6","volume":"74","author":"I Rani","year":"2014","unstructured":"Rani I, Vaiphei K, Agnihotri N. Supplementation of fish oil augments efficacy and attenuates toxicity of 5- fluorouracil in 1,2-dimethylhydrazine dihydrochloride\/dextran sulfate sodium-induced colon carcinogenesis. Cancer Chemother Pharmacol Springer Verlag. 2014;74:309\u201322.","journal-title":"Cancer Chemother Pharmacol"},{"key":"1897_CR18","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1002\/biof.181","volume":"37","author":"RA Siddiqui","year":"2011","unstructured":"Siddiqui RA, Harvey KA, Xu Z, Bammerlin EM, Walker C, Altenburg JD. Docosahexaenoic acid: a natural powerful adjuvant that improves efficacy for anticancer treatment with no adverse effects. BioFactors. 2011;37:399\u2013412.","journal-title":"BioFactors."},{"key":"1897_CR19","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1007\/BF02994764","volume":"26","author":"BT Yu","year":"2003","unstructured":"Yu BT, Sun X, Zhang ZR. Enhanced liver targeting by synthesis of N1-stearyl-5-Fu and incorporation into solid lipid nanoparticles. Arch Pharm Res. 2003;26:1096\u2013101.","journal-title":"Arch Pharm Res"},{"key":"1897_CR20","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/S0022-2836(65)80093-6","volume":"13","author":"AD Bangham","year":"1965","unstructured":"Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol. 1965;13:238\u201352.","journal-title":"J Mol Biol"},{"key":"1897_CR21","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1002\/ijc.10146","volume":"98","author":"S Violette","year":"2002","unstructured":"Violette S, Poulain L, Dussaulx E, Pepin D, Faussat AM, Chambaz J, et al. Resistance of colon cancer cells to long-term 5-fluorouracil exposure is correlated to the relative level of Bcl-2 and Bcl-xL in addition to Bax and p53 status. Int J Cancer. 2002;98:498\u2013504.","journal-title":"Int J Cancer"},{"key":"1897_CR22","doi-asserted-by":"publisher","unstructured":"Dupertuis YM, Delie F, Cohen M, Pichard C. In ovo method for evaluating the effect of nutritional therapies on tumor development, growth and vascularization. Clin Nutr Exp. 2015;2:9\u201317. https:\/\/doi.org\/10.1016\/j.yclnex.2015.08.001.","DOI":"10.1016\/j.yclnex.2015.08.001"},{"key":"1897_CR23","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1021\/jp210088n","volume":"116","author":"S Lopes","year":"2012","unstructured":"Lopes S, Simeonova M, Gameiro P, Rangel M, Ivanova G. Interaction of 5-fluorouracil loaded nanoparticles with 1,2-dimyristoyl-sn-glycero-3-phosphocholine liposomes used as a cellular membrane model. J Phys Chem B. American Chemical Society. 2012;116:667\u201375.","journal-title":"J Phys Chem B"},{"key":"1897_CR24","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1097\/CAD.0b013e328346c7d6","volume":"22","author":"IA Alvi","year":"2011","unstructured":"Alvi IA, Madan J, Kaushik D, Sardana S, Pandey RS, Ali A. Comparative study of transfersomes, liposomes, and niosomes for topical delivery of 5-fluorouracil to skin cancer cells: preparation, characterization, in-vitro release, and cytotoxicity analysis. Anti-Cancer Drugs. 2011;22:774\u201382.","journal-title":"Anti-Cancer Drugs"},{"key":"1897_CR25","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1016\/j.jsps.2019.02.008","volume":"27","author":"A Alomrani","year":"2019","unstructured":"Alomrani A, Badran M, Harisa GI, ALshehry M, Alhariri M, Alshamsan A, et al. The use of chitosan-coated flexible liposomes as a remarkable carrier to enhance the antitumor efficacy of 5-fluorouracil against colorectal cancer. Saudi Pharm J. 2019;27:603\u201311.","journal-title":"Saudi Pharm J"},{"key":"1897_CR26","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1038\/sj.bjc.6603970","volume":"97","author":"R Fanciullino","year":"2007","unstructured":"Fanciullino R, Giacometti S, Mercier C, Aubert C, Blanquicett C, Piccerelle P, et al. In vitro and in vivo reversal of resistance to 5-fluorouracil in colorectal cancer cells with a novel stealth double-liposomal formulation. Br J Cancer. 2007;97:919\u201326.","journal-title":"Br J Cancer"},{"key":"1897_CR27","doi-asserted-by":"publisher","unstructured":"Liko F, Erdo\u011fan S, \u00d6zer YA, Vural I. In vitro studies on 5-florouracil-loaded DTPA-PE containing nanosized pegylated liposomes for diagnosis and treatment of tumor. 2013;23(1):61\u20139. https:\/\/doi.org\/10.3109\/08982104.2012.742538.","DOI":"10.3109\/08982104.2012.742538"},{"key":"1897_CR28","doi-asserted-by":"publisher","unstructured":"Fanciullino R, Mollard S, Giacometti S, Berda-Haddad Y, Chefrour M, Aubert C, et al. In vitro and in vivo evaluation of lipofufol, a new triple stealth liposomal formulation of modulated 5-FU: impact on efficacy and toxicity. Pharm Res. 2013;30(5):1281\u201390. https:\/\/doi.org\/10.1007\/s11095-012-0967-2.","DOI":"10.1007\/s11095-012-0967-2"},{"issue":"4","key":"1897_CR29","doi-asserted-by":"publisher","first-page":"2761","DOI":"10.1016\/j.foodchem.2012.07.016","volume":"135","author":"B Rasti","year":"2012","unstructured":"Rasti B, Jinap S, Mozafari MR, Yazid AM. Comparative study of the oxidative and physical stability of liposomal and nanoliposomal polyunsaturated fatty acids prepared with conventional and Mozafari methods. Food Chem. 2012;135(4):2761\u201370. https:\/\/doi.org\/10.1016\/j.foodchem.2012.07.016.","journal-title":"Food Chem."},{"key":"1897_CR30","doi-asserted-by":"publisher","first-page":"2573","DOI":"10.1271\/bbb.66.2573","volume":"66","author":"M Araseki","year":"2002","unstructured":"Araseki M, Yamamoto K, Miyashita K. Oxidative stability of polyunsaturated fatty acid in phosphatidylcholine liposomes. Biosci Biotechnol Biochem. 2002;66:2573\u20137.","journal-title":"Biosci Biotechnol Biochem"},{"key":"1897_CR31","doi-asserted-by":"publisher","unstructured":"Thomas AM, Kapanen AI, Hare JI, Ramsay E, Edwards K, Karlsson G, et al. Development of a liposomal nanoparticle formulation of 5-fluorouracil for parenteral administration: formulation design, pharmacokinetics and efficacy. J Control Release. Elsevier B.V.; 2011;150:212\u20139. Available from: https:\/\/doi.org\/10.1016\/j.jconrel.2010.11.018","DOI":"10.1016\/j.jconrel.2010.11.018"},{"key":"1897_CR32","doi-asserted-by":"publisher","unstructured":"Dasilva G, Pazos M, Garc\u00eda-Egido E, P\u00e9rez-Jim\u00e9nez J, Torres JL, Giralt M, et al. Lipidomics to analyze the influence of diets with different EPA:DHA ratios in the progression of metabolic syndrome using SHROB rats as a model. Food Chem. Elsevier Ltd; 2016 [cited 2020 Oct 20];205:196\u2013203. Available from: https:\/\/doi.org\/10.1016\/j.foodchem.2016.03.020","DOI":"10.1016\/j.foodchem.2016.03.020"},{"key":"1897_CR33","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.chemphyslip.2018.01.002","volume":"212","author":"SCR Sherratt","year":"2018","unstructured":"Sherratt SCR, Mason RP. Eicosapentaenoic acid and docosahexaenoic acid have distinct membrane locations and lipid interactions as determined by X-ray diffraction. Chem Phys LipidsElsevier Ireland Ltd. 2018;212:73\u20139.","journal-title":"Chem Phys Lipids"},{"key":"1897_CR34","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1089\/ars.2011.4414","volume":"16","author":"SC Gupta","year":"2012","unstructured":"Gupta SC, Hevia D, Patchva S, Park B, Koh W, Aggarwal BB. Upsides and downsides of reactive oxygen species for cancer: the roles of reactive oxygen species in tumorigenesis, prevention, and therapy. Antioxid Redox Signal. 2012;16:1295\u2013322.","journal-title":"Antioxid Redox Signal"},{"key":"1897_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/jcp.10119","volume":"192","author":"JL Martindale","year":"2002","unstructured":"Martindale JL, Holbrook NJ. Cellular response to oxidative stress: signaling for suicide and survival. J Cell Physiol. 2002;192:1\u201315.","journal-title":"J Cell Physiol"},{"key":"1897_CR36","doi-asserted-by":"publisher","first-page":"5119","DOI":"10.1002\/jcp.26356","volume":"233","author":"S Lin","year":"2018","unstructured":"Lin S, Li Y, Zamyatnin AA, Werner J, Bazhin AV. Reactive oxygen species and colorectal cancer. J Cell Physiol. 2018;233:5119\u201332.","journal-title":"J Cell Physiol"},{"key":"1897_CR37","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.colsurfb.2019.04.035","volume":"180","author":"K Sen","year":"2019","unstructured":"Sen K, Banerjee S, Mandal M. Dual drug loaded liposome bearing apigenin and 5-fluorouracil for synergistic therapeutic efficacy in colorectal cancer. Colloids Surf B: Biointerfaces. 2019;180:9\u201322.","journal-title":"Colloids Surf B: Biointerfaces"},{"key":"1897_CR38","doi-asserted-by":"publisher","first-page":"6206","DOI":"10.3748\/wjg.v21.i20.6206","volume":"21","author":"QB Wu","year":"2015","unstructured":"Wu QB, Sun GP. Expression of COX-2 and HER-2 in colorectal cancer and their correlation. World J Gastroenterol. 2015;21:6206\u201314.","journal-title":"World J Gastroenterol"},{"key":"1897_CR39","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1097\/MCO.0b013e3283392656","volume":"13","author":"V Granci","year":"2010","unstructured":"Granci V, Dupertuis YM, Pichard C. Angiogenesis as a potential target of pharmaconutrients in cancer therapy. Curr Opin Clin Nutr Metab Care. 2010;13:417\u201322.","journal-title":"Curr Opin Clin Nutr Metab Care"}],"container-title":["AAPS PharmSciTech"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1208\/s12249-020-01897-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1208\/s12249-020-01897-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1208\/s12249-020-01897-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T01:53:16Z","timestamp":1611885196000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1208\/s12249-020-01897-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["1897"],"URL":"https:\/\/doi.org\/10.1208\/s12249-020-01897-5","relation":{},"ISSN":["1530-9932"],"issn-type":[{"value":"1530-9932","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"3 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"36"}}