Combination therapy with chitosan/siRNA nanoplexes targeting PDGF-D and PDGFR-? reveals anticancer effect in breast cancer

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dc.authoridŞALVA, EMINE/0000-0002-1159-5850
dc.authoridAlan, Saadet/0000-0003-2329-151X
dc.authorwosidŞALVA, EMINE/CAH-3062-2022
dc.authorwosidKabasakal, Levent/E-3503-2019
dc.authorwosidAlan, Saadet/ABH-4282-2020
dc.contributor.authorSalva, Emine
dc.contributor.authorOzbas, Suna
dc.contributor.authorAlan, Saadet
dc.contributor.authorOzkan, Naziye
dc.contributor.authorEkentok-Atici, Ceyda
dc.contributor.authorKabasakal, Levent
dc.contributor.authorAkbuga, Julide
dc.date.accessioned2024-08-04T20:53:15Z
dc.date.available2024-08-04T20:53:15Z
dc.date.issued2023
dc.departmentİnönü Üniversitesien_US
dc.description.abstractBackground: Platelet derived growth factors (PDGF)-D and the expression of its receptor increase in neoplastic progression of cancer. Co-silencing of growth factor and receptor can be suggested as an important strategy for effective cancer therapy. In the present study, we hypothesized that suppression of PDGF-D signaling pathway with small interfering RNAs (siRNAs) targeting both PDGF-D and PDGF receptor (PDGFR)-beta is a promising strategy for anticancer therapy. Methods: Chitosan nanoplexes containing dual and single siRNA were prepared at different weight ratios and controlled by gel retardation assay. Characterization, cellular uptake, gene silencing and invasion studies were performed. The effect of nanoplexes on breast tumor growth, PDGF expression and apoptosis was investigated. Results: We have shown that downregulation of PDGF-D and PDGFR-beta with chitosan/siRNA nanoplex formulations reduced proliferation and invasion in breast cancer cells. In the in vivo breast tumor model, it was determined that the intratumoral administration of chitosan/siPDGF-D/siPDGFR-beta nanoplexes markedly decreased the tumor volume and PDGF-D and PDGFR-beta mRNA and protein expression levels and increased apoptosis. Conclusions: According to the results obtained, we evaluated the effect of PDGF-D and PDGFR-beta on breast tumor development and showed that RNAi-mediated inhibition of this pathway formulated with chitosan nanoplexes can be considered as a new breast cancer therapy strategy.en_US
dc.description.sponsorshipMarmara University Scientific Research Projects Association; [SAG-B-110412-0075]en_US
dc.description.sponsorshipACKNOWLEDGEMENTS This study was supported by Marmara University Scientific Research Projects Association (grant number SAG-B-110412-0075).en_US
dc.identifier.doi10.1002/jgm.3465
dc.identifier.issn1099-498X
dc.identifier.issn1521-2254
dc.identifier.issue2en_US
dc.identifier.pmid36413571en_US
dc.identifier.scopus2-s2.0-85144081675en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.urihttps://doi.org/10.1002/jgm.3465
dc.identifier.urihttps://hdl.handle.net/11616/101064
dc.identifier.volume25en_US
dc.identifier.wosWOS:000896890600001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofJournal of Gene Medicineen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectbreast canceren_US
dc.subjectchitosanen_US
dc.subjectPDGF-Den_US
dc.subjectPDGFR-betaen_US
dc.subjectRNAien_US
dc.titleCombination therapy with chitosan/siRNA nanoplexes targeting PDGF-D and PDGFR-? reveals anticancer effect in breast canceren_US
dc.typeArticleen_US

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