Synergistic inhibition of aggressive breast cancer cell migration and invasion by cytoplasmic delivery of anti-RhoC silencing RNA and presentation of EPPT1 peptide on "smart" particles

dc.authorid0000-0003-2776-5807
dc.contributor.authorKaushal, Neha
dc.contributor.authorTiruchinapally, Gopinath
dc.contributor.authorYüksel Durmaz, Yasemin
dc.contributor.authorBao, Liwei
dc.contributor.authorGilani, Rabia
dc.contributor.authorMerajver, Sofia D.
dc.contributor.authorElSayed, Mohamed E. H.
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T19:57:47Z
dc.date.available10.07.201910:49:13
dc.date.available2019-07-10T19:57:47Z
dc.date.issued2018
dc.departmentİstanbul Medipol Üniversitesi, Mühendislik ve Doğa Bilimleri Fakültesi, Biyomedikal Mühendisliği Bölümü
dc.descriptionWOS: 000448396000009
dc.descriptionPubMed ID: 30149048
dc.description.abstractOverexpression of RhoC protein in breast cancer patients has been linked to increased cancer cell invasion, migration, and metastases. Suppressing RhoC expression in aggressive breast cancer cells using silencing RNA (siRNA) molecules is a viable strategy to inhibit the metastatic spread of breast cancer. In this report, we describe the synthesis of a series of asymmetric pH-sensitive, membrane-destabilizing polymers engineered to complex anti-RhoC siRNA molecules forming "smart" nanoparticles. Using beta-CD as the particle core, polyethylene glycol (PEG) chains were conjugated to the primary face via non-cleavable bonds and amphiphilic polymers incorporating hydrophobic and cationic monomers were grafted to the secondary face via acid-labile linkages. We investigated the effect of PEG molecular weight (2 & 5 kDa) on transfection capacity and serum stability of the formed particles. We evaluated the efficacy of EPPT1 peptides presented on the free tips of the PEG brush to function as a targeting ligand against underglycosylated MUC1 (uMUC1) receptors overexpressed on the surface of metastatic breast cancer cells. Results show that "smart" nanoparticles successfully delivered anti-RhoC siRNA into the cytoplasm of aggressive SUM149 and MDA-MB-231 breast cancer cells, which resulted in a dose-dependent inhibition of cell migration and invasion. Further, EPPT1-targeted nanoparticles demonstrate a synergistic inhibition of cell migration and invasion imparted via RhoC knockdown and EPPT1-mediated signaling via the uMUC1 receptor.
dc.identifier.citationKaushal, N., Tiruchinapally, G., Yüksel Durmaz, Y., Bao, L., Gilani, R., Merajver, S. D. ... ElSayed, M. E. H. (2018). Synergistic inhibition of aggressive breast cancer cell migration and invasion by cytoplasmic delivery of anti-RhoC silencing RNA and presentation of EPPT1 peptide on "smart" particles. Journal of Controlled Release, 289, 79-93. https://dx.doi.org/10.1016/j.jconrel.2018.07.042
dc.identifier.doi10.1016/j.jconrel.2018.07.042
dc.identifier.endpage93
dc.identifier.issn0168-3659
dc.identifier.issn1873-4995
dc.identifier.scopusqualityQ1
dc.identifier.startpage79
dc.identifier.urihttps://dx.doi.org/10.1016/j.jconrel.2018.07.042
dc.identifier.urihttps://hdl.handle.net/20.500.12511/3047
dc.identifier.volume289
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier Science Bv
dc.relation.ispartofJournal of Controlled Releaseen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectPH-Sensitive Polymers
dc.subjectSmart Particles
dc.subjectRhoC Protein
dc.subjectEPPT1/uMUC1 Receptor Interaction
dc.subjectBreast Cancer Cell migration and Invasion
dc.titleSynergistic inhibition of aggressive breast cancer cell migration and invasion by cytoplasmic delivery of anti-RhoC silencing RNA and presentation of EPPT1 peptide on "smart" particles
dc.typeArticle

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