Preparation of dual drug-loaded polymer nanoconjugate to enhance treatment efficacy for ovarian cancer cells

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dc.authorid0000-0003-2659-4129
dc.authorid0000-0002-6593-3237
dc.authorid0000-0003-0612-2263
dc.contributor.authorOzel, Buket
dc.contributor.authorSanlier, Senay
dc.contributor.authorGunduz, Cumhur
dc.contributor.authorGunel, Nur Selvi
dc.date.accessioned2025-04-21T08:31:53Z
dc.date.available2025-04-21T08:31:53Z
dc.date.issued2024
dc.departmentEge Üniversitesi, Tıp Fakültesi, Temel Bilimler Bölümü, Tıbbi Biyoloji Ana Bilim Dalı
dc.description.abstractOvarian cancer is the deadliest gynecological malignancy, representing 2.5 % of all female cancers and accounting for 5 % of female cancer-related fatalities. Despite numerous strategies in its treatment, the disease shows a high recurrence rate and a low survival rate. Consequently, there is a growing focus on targeted therapies in ovarian cancer treatment. It is well-known that VEGFR and LPA pathways undergo alterations in ovarian cancer and stimulate survival, adhesion, migration, invasion, tumor growth and angiogenesis. Cabozantinib (CBZ) is a multi-receptor tyrosine kinase inhibitor that effectively targets MET, VEGFR-1, 2, 3, FLT3, c-KIT, and RET. Ki16425 is a selective inhibitor of LPA receptors 1, 2, and 3. Therefore, targeting LPA receptors and combining with VEGFR inhibitor is a strategic approach for ovarian cancer treatment. In this study, it was aimed to prepare polymer-drug nanoconjugate for both VEGFR and LPAR inhibition. For this, O-(2-Carboxyethyl) polyethylene glycol (PEG5000) 5000 ) which advantages are known in cancer studies, was chosen as the carrier system, and a nanoconjugate containing Ki16425 and CBZ (Ki-PEG-CBZ) was synthesized and its potential was evaluated. Initially, CBZ and Ki16425 were conjugated to the PEG 5000 through pH-sensitive hydrazone and ester bonds. After nanoconjugate characterization, in vitro release and its ovarian cancer treatment potential were evaluated on A2780, OVCAR3 and SKOV3 ovarian cancer cell lines. A nanoconjugate was obtained with a particle size of 169 f 15.23 nm, a zeta potential of-13.5 f 1.21 mV, and a release profile lasting 48 h, containing CBZ and Ki16425 with drug loading efficiencies of 73.71 f 0.53% and 77.72 f 2.51 %, respectively. In vitro studies have demonstrated that Ki-PEG-CBZ is highly effective against ovarian cancer. We suggest that the developed polymer-drug nanoconjugate is an effective and safe nanoconjugate for the treatment of ovarian cancer.
dc.identifier.citationOzel, B., Sanlier, S., Gunduz, C., & Selvi Gunel, N. (2024). Preparation of dual drug-loaded polymer nanoconjugate to enhance treatment efficacy for ovarian cancer cells. European Journal of Pharmaceutics and Biopharmaceutics, 204, 114526.
dc.identifier.doi10.1016/j.ejpb.2024.114526
dc.identifier.endpage15
dc.identifier.issn09396411
dc.identifier.issueNov
dc.identifier.pmid39383976
dc.identifier.scopus2-s2.0-85205974673
dc.identifier.scopusqualityQ1
dc.identifier.startpage1
dc.identifier.urihttps://doi.org/10.1016/j.ejpb.2024.114526
dc.identifier.urihttps://hdl.handle.net/11454/117126
dc.identifier.volume204
dc.identifier.wosWOS:001335133900001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorOzel, Buket
dc.institutionauthorSanlier, Senay
dc.institutionauthorGunduz, Cumhur
dc.institutionauthorGunel, Nur Selvi
dc.institutionauthorid0000-0003-2659-4129
dc.institutionauthorid0000-0002-6593-3237
dc.institutionauthorid0000-0003-0612-2263
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofEuropean Journal of Pharmaceutics and Biopharmaceutics
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectCabozantinib
dc.subjectKi16425
dc.subjectLPA
dc.subjectOvarian cancer
dc.subjectpH-sensetive bonds
dc.subjectPolymer drug nanoconjugate
dc.subjectVEGF
dc.titlePreparation of dual drug-loaded polymer nanoconjugate to enhance treatment efficacy for ovarian cancer cells
dc.typeArticle

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