{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:24Z","timestamp":1787028504088,"version":"build-2736575974"},"reference-count":58,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T00:00:00Z","timestamp":1676937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Cancer Institute (NCI) of the National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["U54CA233396"],"award-info":[{"award-number":["U54CA233396"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Cancer Institute (NCI) of the National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["U54MD007582"],"award-info":[{"award-number":["U54MD007582"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006545","name":"National Institute of Health (NIH) National Institute on Minority Health and Health Disparities (NIMHD)","doi-asserted-by":"publisher","award":["U54CA233396"],"award-info":[{"award-number":["U54CA233396"]}],"id":[{"id":"10.13039\/100006545","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006545","name":"National Institute of Health (NIH) National Institute on Minority Health and Health Disparities (NIMHD)","doi-asserted-by":"publisher","award":["U54MD007582"],"award-info":[{"award-number":["U54MD007582"]}],"id":[{"id":"10.13039\/100006545","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Title III of Florida A&amp;M University","award":["U54CA233396"],"award-info":[{"award-number":["U54CA233396"]}]},{"name":"Title III of Florida A&amp;M University","award":["U54MD007582"],"award-info":[{"award-number":["U54MD007582"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pancreatic cancer is projected to be the second leading cause of cancer-related death by 2030 in the US. The benefits of the most common systemic therapy for various pancreatic cancers have been masked by high drug toxicities, adverse reactions, and resistance. The use of nanocarriers such as liposomes to overcome these unwanted effects has become very popular. This study aims to formulate 1,3-bistertrahydrofuran-2yl-5FU (MFU)-loaded liposomal nanoparticles (Zhubech) and to evaluate itsstability, release kinetics, in vitro and in vivo anticancer activities, and biodistribution in different tissues. Particle size and zeta potential were determined using a particle size analyzer, while cellular uptake of rhodamine-entrapped liposomal nanoparticles (Rho-LnPs) was determined by confocal microscopy. Gadolinium hexanoate (Gd-Hex) was synthesized and entrapped into the liposomal nanoparticle (LnP) (Gd-Hex-LnP), as a model contrast agent, to evaluate gadolinium biodistribution and accumulation by LnPs in vivo using inductively coupled plasma mass spectrometry (ICP-MS). The mean hydrodynamic diameters of blank LnPs and Zhubech were 90.0 \u00b1 0.65 nm and 124.9 \u00b1 3.2 nm, respectively. The hydrodynamic diameter of Zhubech was found to be highly stable at 4 \u00b0C and 25 \u00b0C for 30 days in solution. In vitro drug release of MFU from Zhubech formulation exhibited the Higuchi model (R2 value = 0.95). Both Miapaca-2 and Panc-1 treated with Zhubech showed reduced viability, two- or four-fold lower than that of MFU-treated cells in 3D spheroid (IC50Zhubech = 3.4 \u00b1 1.0 \u03bcM vs. IC50MFU = 6.8 \u00b1 1.1 \u03bcM) and organoid (IC50Zhubech = 9.8 \u00b1 1.4 \u03bcM vs. IC50MFU = 42.3 \u00b1 1.0 \u03bcM) culture models. Confocal imaging confirmed a high uptake of rhodamine-entrapped LnP by Panc-1 cells in a time-dependent manner. Tumor-efficacy studies in a PDX bearing mouse model revealed a more than 9-fold decrease in mean tumor volumes in Zhubech-treated (108 \u00b1 13.5 mm3) compared to 5-FU-treated (1107 \u00b1 116.2 mm3) animals, respectively. This study demonstrates that Zhubech may be a potential candidate for delivering drugs for pancreatic cancer treatment.<\/jats:p>","DOI":"10.3390\/ijms24054288","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T03:32:17Z","timestamp":1677036737000},"page":"4288","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Evaluation of Anticancer Activity of Zhubech, a New 5-FU Analog Liposomal Formulation, against Pancreatic Cancer"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5825-2022","authenticated-orcid":false,"given":"Nkafu Bechem","family":"Ndemazie","sequence":"first","affiliation":[{"name":"College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raviteja","family":"Bulusu","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue You","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6908-823X","authenticated-orcid":false,"given":"Esther Kesewaah","family":"Frimpong","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andriana","family":"Inkoom","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy","family":"Okoro","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dexter","family":"Ebesoh","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, University of Buea, Buea P.O. Box 63, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherise","family":"Rogers","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Florida, Gainesville, FL 32608, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1458-4265","authenticated-orcid":false,"given":"Bo","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Surgery, Keck School of Medicine University of South California, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Agyare","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,21]]},"reference":[{"key":"ref_1","unstructured":"Murphy, S.L., Kochanek, K.D., Xu, J., and Arias, E. (2021). Mortality in the United States, 2020."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/1556-276X-8-102","article-title":"Liposome: Classification, preparation, and applications","volume":"8","author":"Akbarzadeh","year":"2013","journal-title":"Nanoscale Res. Lett."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Bulbake, U., Doppalapudi, S., Kommineni, N., and Khan, W. (2017). Liposomal Formulations in Clinical Use: An Updated Review. Pharmaceutics, 9.","DOI":"10.3390\/pharmaceutics9020012"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s13045-021-01096-0","article-title":"Nanomaterials for cancer therapy: Current progress and perspectives","volume":"14","author":"Cheng","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"26580","DOI":"10.1073\/pnas.1911273116","article-title":"Pancreatic cancer organoids recapitulate disease and allow personalized drug screening","volume":"116","author":"Driehuis","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1208\/s12249-021-02144-1","article-title":"Multi-disciplinary Approach for Drug and Gene Delivery Systems to the Brain","volume":"23","author":"Ndemazie","year":"2021","journal-title":"AAPS PharmSciTech"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/s41568-018-0007-6","article-title":"Organoids in cancer research","volume":"18","author":"Drost","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1208\/s12249-020-01897-5","article-title":"Antitumor Effect of 5-Fluorouracil-Loaded Liposomes Containing n-3 Polyunsaturated Fatty Acids in Two Different Colorectal Cancer Cell Lines","volume":"22","author":"Dupertuis","year":"2021","journal-title":"AAPS Pharmscitech"},{"key":"ref_9","unstructured":"Gracia, B. (2019). Cancer Nanotechnology, Springer."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.jconrel.2004.09.001","article-title":"Preparation, characterization, cytotoxicity and pharmacokinetics of liposomes containing lipophilic gemcitabine prodrugs","volume":"100","author":"Immordino","year":"2004","journal-title":"J. Control. Release"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"122022","DOI":"10.1016\/j.ijpharm.2022.122022","article-title":"Stability characterization for pharmaceutical liposome product development with focus on regulatory considerations: An update","volume":"624","author":"Bulusu","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2964","DOI":"10.7150\/ijms.49801","article-title":"Application of nanotechnology in cancer diagnosis and therapy-a mini-review","volume":"17","author":"Jin","year":"2020","journal-title":"Int. J. Med. Sci."},{"key":"ref_13","unstructured":"Bulbake, U., Kommineni, N., and Khan, W. (2020). Handbook of Materials for Nanomedicine, Jenny Stanford Publishing."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.jconrel.2011.09.066","article-title":"In vivo antitumor effect of cromolyn in PEGylated liposomes for pancreatic cancer","volume":"157","author":"Kim","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"122","DOI":"10.5507\/bp.2019.010","article-title":"Nanodrugs used in cancer therapy","volume":"163","author":"Kopeckova","year":"2019","journal-title":"Biomed. Pap. Med. Fac. Palacky Univ. Olomouc"},{"key":"ref_16","first-page":"100056","article-title":"Enhancing efficacy of gemcitabine in pancreatic patient-derived xenograft mouse models","volume":"2","author":"Inkoom","year":"2020","journal-title":"Int. J. Pharm. X"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Khattak, M.I.K., Ahmed, N., Umer, M.F., Riaz, A., Ahmad, N.M., and Khan, G.M. (2020). Chloroform-Injection (CI) and Spontaneous-Phase-Transition (SPT) Are Novel Methods, Simplifying the Fabrication of Liposomes with Versatile Solution to Cholesterol Content and Size Distribution. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12111065"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2858","DOI":"10.1021\/acs.molpharmaceut.8b01284","article-title":"Development of liposomal gemcitabine with high drug loading capacity","volume":"16","author":"Tamam","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"424","DOI":"10.7150\/ntno.76370","article-title":"Stealth Liposomal Chemotherapeutic Agent for Triple Negative Breast Cancer with Improved Pharmacokinetics","volume":"6","author":"Kommineni","year":"2022","journal-title":"Nanotheranostics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"611","DOI":"10.3892\/or.2017.5718","article-title":"Cancer drug delivery in the nano era: An overview and perspectives","volume":"38","author":"Li","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.addr.2015.09.012","article-title":"PEGylation as a strategy for improving nanoparticle-based drug and gene delivery","volume":"99","author":"Suk","year":"2016","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1007\/s11095-021-03045-5","article-title":"A Liposomal Gemcitabine, FF-10832, Improves Plasma Stability, Tumor Targeting, and Antitumor Efficacy of Gemcitabine in Pancreatic Cancer Xenograft Models","volume":"38","author":"Matsumoto","year":"2021","journal-title":"Pharm. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.jcmgh.2017.12.004","article-title":"Pancreas 3D organoids: Current and future aspects as a research platform for personalized medicine in pancreatic cancer","volume":"5","author":"Moreira","year":"2018","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1039\/c0nr00132e","article-title":"Liposomal squalenoyl-gemcitabine: Formulation, characterization and anticancer activity evaluation","volume":"2","author":"Pili","year":"2010","journal-title":"Nanoscale"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41392-017-0004-3","article-title":"Controlled drug delivery vehicles for cancer treatment and their performance","volume":"3","author":"Senapati","year":"2018","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1007\/s11095-016-1902-8","article-title":"Development of long-circulating pH-sensitive liposomes to circumvent gemcitabine resistance in pancreatic cancer cells","volume":"33","author":"Xu","year":"2016","journal-title":"Pharm. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.ctrv.2011.01.006","article-title":"Liposome based delivery systems in pancreatic cancer treatment: From bench to bedside","volume":"37","author":"Yang","year":"2011","journal-title":"Cancer Treat. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ndemazie, N.B., Inkoom, A., Ebesoh, D., Bulusu, R., Frimpong, E., Trevino, J., Han, B., Zhu, X., and Agyare, E. (2022). Synthesis, characterization, and in vitro anticancer evaluation of 1, 3-bistetrahydrofuran-2yl-5-FU as a potential agent for pancreatic cancer. BMC Cancer, 22.","DOI":"10.1186\/s12885-022-10449-y"},{"key":"ref_29","first-page":"245","article-title":"Cytotoxicity of 5-fluorouracil-loaded pH-sensitive liposomal nanoparticles in colorectal cancer cell lines","volume":"2","author":"Udofot","year":"2015","journal-title":"Integr. Cancer Sci. Ther."},{"key":"ref_30","first-page":"e171","article-title":"Pharmacokinetic, biodistribution and therapeutic efficacy of 5-fluorouracil-loaded pH-sensitive PEGylated liposomal nanoparticles in HCT-116 tumor bearing mouse","volume":"2","author":"Udofot","year":"2016","journal-title":"J. Nat. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1080\/03639040601011215","article-title":"Formulation Development and Stability Studies of Aqueous Metronidazole Benzoate Suspensions Containing Various Suspending Agents","volume":"33","author":"Zietsman","year":"2007","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1128\/AAC.42.4.762","article-title":"Amphotericin B in lipid emulsion: Stability, compatibility, and in vitro antifungal activity","volume":"42","author":"Walker","year":"1998","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1081\/DDC-120018380","article-title":"Preparation, Optimization, Characterization, and Stability Studies of Salicylic Acid Liposomes","volume":"29","author":"Bhalerao","year":"2003","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"de Almeida Campos, L., Fin, M.T., Santos, K.S., de Lima Gualque, M.W., Freire Cabral, A.K.L., Khalil, N.M., Fusco-Almeida, A.M., Mainardes, R.M., and Mendes-Giannini, M.J.S. (2023). Nanotechnology-Based Approaches for Voriconazole Delivery Applied to Invasive Fungal Infections. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15010266"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.ijpharm.2013.04.044","article-title":"Mathematical modeling of drug dissolution","volume":"453","author":"Siepmann","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.ijpharm.2011.03.051","article-title":"Higuchi equation: Derivation, applications, use and misuse","volume":"418","author":"Siepmann","year":"2011","journal-title":"Int. J. Pharm."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.ijpharm.2007.07.012","article-title":"Cellular uptake of solid lipid nanoparticles and cytotoxicity of encapsulated paclitaxel in A549 cancer cells","volume":"348","author":"Yuan","year":"2008","journal-title":"Int. J. Pharm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7538","DOI":"10.1038\/s41598-018-25878-8","article-title":"Understanding the connection between nanoparticle uptake and cancer treatment efficacy using mathematical modeling","volume":"8","author":"Brocato","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e3131","DOI":"10.21769\/BioProtoc.3131","article-title":"Evaluation of anticancer activity of silver nanoparticles on the A549 human lung carcinoma cell lines through alamar blue assay","volume":"9","author":"Sharma","year":"2019","journal-title":"Bio-Protocol"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1038\/sj.bjc.6600317","article-title":"Anti-tumour activity and toxicity of the new prodrug9-aminocamptothecin glucuronide (9ACG) in mice","volume":"86","author":"Prijovich","year":"2002","journal-title":"Br. J. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1080\/17425247.2020.1737672","article-title":"The latest advances of cisplatin liposomal formulations: Essentials for preparation and analysis","volume":"17","author":"Zahednezhad","year":"2020","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_42","first-page":"737","article-title":"The influence of temperature, cholesterol content and pH on liposome stability","volume":"744","author":"Pentak","year":"2005","journal-title":"J. Mol. Struct."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"120051","DOI":"10.1016\/j.ijpharm.2020.120051","article-title":"Comprehensive analysis of liposome formulation parameters and their influence on encapsulation, stability and drug release in glibenclamide liposomes","volume":"592","author":"Maritim","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_44","unstructured":"Schwendener, R.A., and Schott, H. (2010). Liposomes, Springer."},{"key":"ref_45","unstructured":"Bruschi, M.L. (2015). Mathematical Models of Drug Release, Woodhead Publishing."},{"key":"ref_46","first-page":"217","article-title":"Kinetic modeling on drug release from controlled drug delivery systems","volume":"67","author":"Dash","year":"2010","journal-title":"Acta Pol. Pharm."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jconrel.2010.08.026","article-title":"Peritoneal retention of liposomes: Effects of lipid composition, PEG coating and liposome charge","volume":"148","author":"Dadashzadeh","year":"2010","journal-title":"J. Control. Release"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/08982104.2017.1391285","article-title":"Microfluidic preparation of drug-loaded PEGylated liposomes, and the impact of liposome size on tumour retention and penetration","volume":"29","author":"Dong","year":"2019","journal-title":"J. Liposome Res."},{"key":"ref_49","first-page":"1206","article-title":"Liposomal and nonliposomal drug pharmacokinetics after administration of liposome-encapsulated vincristine and their contribution to drug tissue distribution properties","volume":"298","author":"Krishna","year":"2001","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3109\/08982104.2012.655285","article-title":"Factors affecting the pharmacokinetics and pharmacodynamics of liposomal drugs","volume":"22","author":"Song","year":"2012","journal-title":"J. Liposome Res."},{"key":"ref_51","first-page":"96","article-title":"Localized drug delivery using crosslinked gelatin gels containing liposomes: Factors influencing liposome stability and drug release","volume":"51","author":"DiTizio","year":"2000","journal-title":"J. Biomed. Mater. Res. Off. J. Soc. Biomater. Jpn. Soc. Biomater. Aust. Soc. Biomater. Korean Soc. Biomater."},{"key":"ref_52","unstructured":"Zhang, H. (2017). Liposomes, Springer."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5728","DOI":"10.1021\/acs.langmuir.8b00411","article-title":"Paclitaxel-loaded pH-sensitive liposome: New insights on structural and physicochemical characterization","volume":"34","author":"Monteiro","year":"2018","journal-title":"Langmuir"},{"key":"ref_54","first-page":"26","article-title":"In vitro permeation and stability studies on developed drug-in-adhesive transdermal patch of simvastatin","volume":"56","author":"Parhi","year":"2018","journal-title":"Bull. Fac. Pharm. Cairo Univ."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.tips.2009.08.004","article-title":"Liposomes and nanoparticles: Nanosized vehicles for drug delivery in cancer","volume":"30","author":"Malam","year":"2009","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s13346-015-0220-8","article-title":"Influence of cholesterol on liposome stability and on in vitro drug release","volume":"5","author":"Briuglia","year":"2015","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_57","unstructured":"Han, B. (2018). MicroRNA Protocols, Springer."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1016\/j.ajpath.2015.01.016","article-title":"Patient-derived xenograft models for pancreatic adenocarcinoma demonstrate retention of tumor morphology through incorporation of murine stromal elements","volume":"185","author":"Delitto","year":"2015","journal-title":"Am. J. Pathol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/5\/4288\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:38:15Z","timestamp":1760121495000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/5\/4288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,21]]},"references-count":58,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijms24054288"],"URL":"https:\/\/doi.org\/10.3390\/ijms24054288","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202301.0177.v1","asserted-by":"object"}]},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,21]]}}}