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  • Küçük Resim
    Öğe
    Development of light and pH-dual responsive self-quenching theranostic SPION to make EGFR overexpressing micro tumors glow and destroy
    (Elsevier B.V., 2023) Verimli, Nihan; Goralı, Selen İrem; Abişoğlu, Beyza; Altan, Cem Levent; Sucu, Bilgesu Onur; Karataş, Ersin; Tülek, Ahmet; Bayraktaroğlu, Çiğdem; Beker, Mustafa Çağlar; Erdem, Sultan Sibel
    Drug 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.
  • Küçük Resim
    Öğe
    Glow in the dark tumor: enhanced near-ir visualization and destruction of cancer with a self-quenched theranostic
    (2025) Güler, Selen İrem; Altan, Cem Levent; Demircioğlu, Emine Esma; Verimli, Nihan; Abisoğlu, Beyza; Bayraktaroğlu, Çiğdem; Erdem, Sultan Sibel
    Late diagnosis is one of the major obstacles for the treatment of breast cancer which can be overcome with a system offering sensitive imaging and selective therapeutic effect. In this study, we developed a “dark-bright” multifunctional drug delivery system bringing real-time imaging and non-invasive therapy together. Theranostic ability of the system was delivered by Verteporfin (VP), serving as a fluorescence probe and a photosensitizer. To create a “dark state” system via self-quenching ability of VP, it was immobilized onto the superparamagnetic iron oxide nanoparticle (SPION) surface. Upon cellular uptake of the “dark state” system, release of VP led to fluorescence regain, switching the system to “bright state” after which photodynamic therapy (PDT) was initiated to lead to cell death. Theranostic feature of the system was evaluated in MCF-7 and MDA-MB-231 cell lines. Following internalization, fluorescence signal was increased up to ∼56-fold in MCF-7 cells. The IC50 value decreased ∼20-fold and ∼117-fold in MCF-7 and MDA-MB-231 cell lines, respectively. Moreover, the system significantly inhibited migration in the highly aggressive MDA-MB-231 cell line and induced apoptosis by caspase-3 activation. The developed “dark-bright” system is a promising multifunctional drug delivery vehicle with extraordinary theranostic features for the detection and destruction of micro tumors.