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

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dc.authorid0000-0002-1693-9579
dc.contributor.authorŞalva, Emine
dc.contributor.authorÖzbaş, Suna
dc.contributor.authorAlan, Saadet
dc.contributor.authorÖzkan, Naziye
dc.contributor.authorEkentok Atıcı, Ceyda
dc.contributor.authorKabasakal, Levent
dc.contributor.authorAkbuğa, Jülide
dc.date.accessioned2023-09-21T05:54:32Z
dc.date.available2023-09-21T05:54:32Z
dc.date.issued2023
dc.departmentİstanbul Medipol Üniversitesi, Eczacılık Fakültesi, Eczacılık Teknolojisi Bölümü, Farmasötik Teknoloji Ana Bilim Dalı
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.
dc.description.sponsorshipMarmara Universityen_US
dc.identifier.citationŞalva, E., Özbaş, S., Alan, S., Özkan, N., Ekentok Atıcı, C., Kabasakal, L. ... Akbuğa, J. (2023). Combination therapy with chitosan/siRNA nanoplexes targeting PDGF-D and PDGFR-beta reveals anticancer effect in breast cancer. Journal of Gene Medicine, 25(2). https://doi.org/10.1002/jgm.3465
dc.identifier.doi10.1002/jgm.3465
dc.identifier.issn1099-498X
dc.identifier.issn1521-2254
dc.identifier.issue2
dc.identifier.pmid36413571
dc.identifier.scopus2-s2.0-85144081675
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://doi.org/10.1002/jgm.3465
dc.identifier.urihttps://hdl.handle.net/20.500.12511/11472
dc.identifier.volume25
dc.identifier.wos000896890600001en_US
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorAkbuğa, Jülide
dc.language.isoen
dc.publisherWiley
dc.relation.ispartofJournal of Gene Medicineen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectBreast Cancer
dc.subjectChitosan
dc.subjectPDGF-D
dc.subjectPDGFR-?
dc.subjectRNAi
dc.titleCombination therapy with chitosan/siRNA nanoplexes targeting PDGF-D and PDGFR-beta reveals anticancer effect in breast cancer
dc.title.alternativeCombination therapy with chitosan/siRNA nanoplexes targeting PDGF-D and PDGFR-? reveals anticancer effect in breast cancer
dc.typeArticle

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