Development of light and pH-dual responsive self-quenching theranostic SPION to make EGFR overexpressing micro tumors glow and destroy

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dc.authorid0000-0001-6829-3960
dc.authorid0000-0003-0957-6965
dc.authorid0000-0002-7318-4053
dc.authorid0000-0002-9476-8488
dc.authorid0000-0001-6876-3555
dc.contributor.authorVerimli, Nihan
dc.contributor.authorGoralı, Selen İrem
dc.contributor.authorAbişoğlu, Beyza
dc.contributor.authorAltan, Cem Levent
dc.contributor.authorSucu, Bilgesu Onur
dc.contributor.authorKarataş, Ersin
dc.contributor.authorTülek, Ahmet
dc.contributor.authorBayraktaroğlu, Çiğdem
dc.contributor.authorBeker, Mustafa Çağlar
dc.contributor.authorErdem, Sultan Sibel
dc.date.accessioned2023-11-10T11:56:03Z
dc.date.available2023-11-10T11:56:03Z
dc.date.issued2023
dc.departmentİstanbul Medipol Üniversitesi, Uluslararası Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyokimya Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Sağlık Bilim ve Teknolojileri Araştırma Enstitüsü
dc.departmentİstanbul Medipol Üniversitesi, Eczacılık Fakültesi, Eczacılık Meslek Bilimleri Bölümü, Farmasötik Kimya Ana Bilim Dalı
dc.description.abstractDrug resistant and undetectable tumors easily escape treatment leading metastases and/or recurrence of the lethal disease. Therefore, it is vital to diagnose and destroy micro tumors using simple yet novel approaches. Here, we present fluorescence-based detection and light-based destruction of cancer cells that are known to be resistant to standard therapies. We developed a superparamagnetic iron oxide nanoparticle (SPION)-based theranostic agent that is composed of self-quenching light activated photosensitizer (BPD) and EGFR targeting ligand (Anti-EGFR ScFv or GE11 peptide). Photosensitizer (BPD) was immobilized to PEG-PEI modified SPION with acid-labile linker. Prior to stimulation of the theranostic system by light its accumulation within cancer cells is vital since BPD phototoxicity and fluorescence is activated by lysosomal proteolysis. As BPD is cleaved, the system switches from off to on position which triggers imaging and therapy. Targeting, therapeutic and diagnostic features of the theranostic system were evaluated in high and moderate level EGFR expressing pancreatic cancer cell lines. Our results indicate that the system distinguishes high and moderate EGFR expression levels and yields up to 4.3-fold increase in intracellular fluorescence intensity. Amplification of fluorescence signal was as low as 1.3-fold in the moderate or no EGFR expressing cell lines. Anti-EGFR ScFv targeted SPION caused nearly 2-fold higher cell death via apoptosis in high EGFR expressing Panc-1 cell line. The developed system, possessing advanced targeting, enhanced imaging and effective therapeutic features, is a promising candidate for multi-mode detection and destruction of residual drug-resistant cancer cells.
dc.identifier.citationVerimli, N., Goralı, S. İ., Abişoğlu, B., Altan, C. L., Sucu, B. O., Karataş, E. ... Erdem, S. S. (2023). Development of light and pH-dual responsive self-quenching theranostic SPION to make EGFR overexpressing micro tumors glow and destroy. Journal of Photochemistry and Photobiology B: Biology, 248. https://dx.doi.org/10.1016/j.jphotobiol.2023.112797
dc.identifier.doi10.1016/j.jphotobiol.2023.112797
dc.identifier.issn1011-1344
dc.identifier.issn1873-2682
dc.identifier.pmid37862898
dc.identifier.scopus2-s2.0-85175211073
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://dx.doi.org/10.1016/j.jphotobiol.2023.112797
dc.identifier.urihttps://hdl.handle.net/20.500.12511/11759
dc.identifier.volume248
dc.identifier.wos001103790900001en_US
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorVerimli, Nihan
dc.institutionauthorGoralı, Selen İrem
dc.institutionauthorSucu, Bilgesu Onur
dc.institutionauthorBayraktaroğlu, Çiğdem
dc.institutionauthorBeker, Mustafa Çağlar
dc.institutionauthorErdem, Sultan Sibel
dc.language.isoen
dc.publisherElsevier B.V.
dc.relation.ispartofJournal of Photochemistry and Photobiology B: Biologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.relation.tubitakinfo:eu-repo/grantAgreement/TUBITAK/SOBAG/118S299
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectEGFR Targeting
dc.subjectFluorescence Imaging
dc.subjectPancreatic Cancer
dc.subjectPhotodyanmic Therapy
dc.subjectSPION
dc.subjectTheranostics
dc.titleDevelopment of light and pH-dual responsive self-quenching theranostic SPION to make EGFR overexpressing micro tumors glow and destroy
dc.typeArticle

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