WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7150
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Article Anticancer Properties of Newly Synthesized Pyrrole Derivatives as Potential Tyrosine Kinase Inhibitors(Wiley, 2026) Şanlı Mohamed, Gülşah; Kara, Yunus; Sanli-Mohamed, Gulsah; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of TechnologyThe anticancer activity of a series of newly synthesized pyrrole derivatives was systematically evaluated in HeLa cervical cancer cells, focusing on their potential as tyrosine kinase inhibitors and modulators of the mTOR signaling pathway. This study builds on our previous synthetic work by investigating the biological effects of seven structurally characterized compounds (d1-d7). Among them, compounds d1 and d3 exhibited the most potent cytotoxicity, with IC50 values of 140.6 mu M and 366.4 mu M, respectively, after 48 h of treatment. Both compounds significantly impaired cell cycle progression-d1 induced S-phase arrest, while d3 caused G1-phase arrest-and markedly suppressed cell migration in wound healing assays. Mechanistically, these effects were accompanied by reduced phosphorylation of p70S6K (Thr389, Ser421/424) and increased p-4EBP1, indicating inhibition of mTORC1 signaling. These findings suggest that d1 and d3 are promising lead compounds with dual antiproliferative and anti-migratory activity in cervical cancer, mediated through modulation of the PI3K/Akt/mTOR axis.Article Encapsulation of IR783 in UiO-66 MOFs for Improved Photodynamic Efficacy Against Breast Cancer Cells(OICC Press, 2025) Şanlı Mohamed, Gülşah; Sanli-Mohamed, Gulsah; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of TechnologyBreast cancer remains the most prevalent malignancy among women worldwide, underscoring the need for innovative therapeutic strategies beyond conventional modalities. Photodynamic therapy (PDT) offers a non-invasive approach that leverages light-activated photosensitizers to induce reactive oxygen species (ROS)-mediated tumor cell death. IR783, a near-infrared fluorescent (NIRF) heptamethine cyanine dye, has shown promise as a theranostic agent in cancer therapy due to its tumor-selective uptake and pro-apoptotic effects. However, its clinical potential is hindered by poor stability, rapid dissociation in polar environments, low quantum yield, and suboptimal tumor accumulation. In this study, we developed a multifunctional nanoplatform by encapsulating IR783 into UiO-66, a zirconium-based metal-organic framework (MOF), to enhance the delivery and photodynamic performance of the dye (IR783@UiO-66). The system was structurally characterized, and its biocompatibility and drug release profiles were evaluated. In vitro experiments were conducted to assess the cytotoxic and phototoxic effects of IR783, UiO-66, and IR783@UiO-66 on breast cancer cell lines (MCF-7, MDA-MB-231) and normal breast epithelial cells (MCF-10A), under LED irradiation at varying light intensities (18-144 J/cm2) and exposure durations (7.5-60 min). The results demonstrated that IR783@UiO-66 significantly reduced cancer cell viability in a dose-and light-dependent manner while sparing normal cells. Free IR783 showed slightly higher phototoxicity, attributed to differences in release kinetics and loading efficiency. UiO-66 alone exhibited negligible cytotoxicity under irradiation, confirming its safety profile. This study highlights the potential of UiO-66 as a promising nanocarrier for enhancing IR783-mediated PDT, offering a synergistic strategy for targeted and efficient breast cancer therapy.Article Lapatinib-Loaded ZIF-8 Nanoparticles: a Multifunctional Drug Delivery System With Anticancer, Antibacterial, and Antioxidant Properties(American Chemical Society, 2025) Şanlı Mohamed, Gülşah; Sanli-Mohamed, Gulsah; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of TechnologyThe pitfalls of conventional chemotherapy, including poor solubility, off-target toxicity, and multidrug resistance, have driven the development of nanoparticle-based delivery systems. Here, we report the facile one-pot synthesis of lapatinib-encapsulated zeolitic imidazolate framework-8 (LAP@ZIF-8) nanoparticles. The formulation achieved an encapsulation efficiency of 72.4% and a drug loading capacity of 6.6%. Comprehensive physicochemical characterization confirmed uniform hexagonal morphology (SEM), favorable hydrodynamic size (236 +/- 2 nm; DLS), positive surface charge (+29 mV; zeta-potential), high crystallinity (XRD), and excellent thermal stability (TGA). LAP release was pH-responsive, with similar to 77% cumulative release at pH 5.5 (tumor-mimicking) versus 43% at pH 7.4 after 96 h. Serum-protein binding (<11%) and hemolysis (<2%) assays demonstrated good biocompatibility. In vitro, LAP@ZIF-8 exhibited potent, selective cytotoxicity toward HER2-positive SK-BR-3 breast-cancer cells (72 h IC50 = 1.2 mu g mL-1) while sparing HER2-negative MCF-7 cells. Importantly, both free LAP and LAP@ZIF-8 were well-tolerated by nontumorigenic MCF-10A mammary epithelial cells: viability remained >= 90% at <= 1 mu g mL-1 and exceeded 50% even at 100 mu g mL-1, indicating that the IC50 was not reached and providing a preliminary safety window for healthy tissues. Beyond its anticancer effects, the nanocarrier displayed broad-spectrum antibacterial activity (minimum bactericidal concentrations: 5 mg mL-1 for Staphylococcus aureus and 10 mg mL-1 for Escherichia coli) and moderate antioxidant capacity (DPPH IC50 = 666 mu g mL-1). Collectively, these results position LAP@ZIF-8 as a versatile, pH-sensitive platform that combines selective anticancer efficacy with low toxicity to healthy cells alongside ancillary antibacterial and antioxidant properties suitable for multimodal therapy.Article Citation - WoS: 1Citation - Scopus: 1Structural and Functional Tuning of ZIF-8 Nanoparticles Via Zinc Salt Variation and Ligand Ratio for Enhanced Drug Delivery(Springer, 2025) Mete, Derya; Şanlı Mohamed, Gülşah; 01. Izmir Institute of Technology; 04. Faculty of Science; 04.01. Department of ChemistryThe clinical application of doxorubicin (DOX), a widely used chemotherapeutic agent, is limited by systemic toxicity, rapid clearance, and the development of multidrug resistance. Metal-organic frameworks (MOFs), particularly zeolitic imidazolate frameworks (ZIFs), have emerged as promising nanocarriers to overcome these limitations due to their high drug-loading capacity, pH-responsive release profiles, and favorable biocompatibility. Among them, ZIF-8 is especially attractive for its ability to selectively release drugs in acidic tumor microenvironments. However, the physicochemical and biological properties of ZIF-8 are highly sensitive to synthesis parameters, particularly the choice of zinc salt precursor and the Zn2+:ligand molar ratio. In this study, we systematically investigated the effects of four zinc salts (zinc nitrate, zinc acetate, zinc chloride, and zinc bromide) and three Zn2+:2-methylimidazole molar ratios (1:35, 1:70, and 1:200) on the synthesis, drug-loading efficiency, release behavior, and anticancer activity of DOX-loaded ZIF-8 (DOX@ZIF-8) nanoparticles. The resulting nanocarriers were characterized using scanning electron microscopy (SEM), dynamic light scattering (DLS), energy-dispersive X-ray spectroscopy (EDX), inductively coupled plasma optical emission spectroscopy (ICP-OES), thermogravimetric analysis (TGA), and Brunauer-Emmett-Teller (BET) surface area analysis. pH-responsive DOX release was evaluated under physiological (pH 7.4) and acidic (pH 5.0) conditions. Cytotoxicity was assessed in A549 lung cancer cells via the MTT assay. Additionally, in vitro time-lapse live-cell imaging and wound healing assays were conducted to evaluate intracellular drug uptake and cellular responses. Our findings highlight the critical influence of zinc salt selection and ligand ratio on the structure-property-function relationships of ZIF-8, providing valuable insights for the rational design of MOF-based nanocarriers in targeted cancer therapy.