Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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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.Article Enhanced Doxorubicin Cytotoxicity on Breast Cancer Spheroids by Aptamer Targeted Co-Delivery With Hyaluronidase(Wiley, 2025) Ahmetoğlu, Çekdar Vakıf; Demirel, Dide Su; Bonyadi, Farzaneh; Guner, Buket Cakmak; Dursun, Ali Dogan; Vakifahmetoglu, Cekdar; Ozalp, Veli Cengiz; 03.09. Department of Materials Science and Engineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyBreast cancer is one of the most prevalent solid tumors in women and can be classified into subtypes based on molecular characteristics, such as hormone receptor status and HER2 expression. Aptamers, highly specific affinity molecules, are extensively studied for targeted drug delivery using nanocarriers to enhance anti-cancer efficacy. This study focused on HER2-responsive co-delivery of doxorubicin and hyaluronidase via aptamer-gated mesoporous silica nanoparticles to improve therapeutic outcomes in solid tumors. SK-BR-3 spheroids are employed as a model for resistant tumor environments in solid tumors. Previous research is shown that conjugating cytotoxic drugs with nanoparticles or cells enhances drug penetration into tumor spheroids. In this work, doxorubicin is loaded into mesoporous silica nanoparticles and capped with HER2-specific aptamers, while the particle surface is functionalized with hyaluronidase. This dual-functionalized nanocarrier system achieves an approximate to 8.5-fold increase in cytotoxicity compared to aptamer-targeted delivery lacking hyaluronidase. The enhanced effect is attributed to hyaluronidase-mediated loosening of the spheroid structure, facilitating nanoparticle penetration and localized release of doxorubicin at high concentrations on HER2-positive cells.Article Citation - Scopus: 13Her2-Targeted, Degradable Core Cross-Linked Micelles for Specific and Dual Ph-Sensitive Dox Release(John Wiley and Sons Inc, 2022) Bayram, N.N.; Baran, Yusuf; Ulu, Gizem Tuğçe; Topuzoğulları, M.; Baran, Y.; Dinçer, İşoğlu, S.; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of Technology; 01.01. Units Affiliated to the RectorateHere, a targeted, dual-pH responsive, and stable micelle nanocarrier is designed, which specifically selects an HER2 receptor on breast cancer cells. Intracellularly degradable and stabilized micelles are prepared by core cross-linking via reversible addition−fragmentation chain-transfer (RAFT) polymerization with an acid-sensitive cross-linker followed by the conjugation of maleimide–doxorubicin to the pyridyl disulfide-modified micelles. Multifunctional nanocarriers are obtained by coupling HER2-specific peptide. Formation of micelles, addition of peptide and doxorubicin (DOX) are confirmed structurally by spectroscopical techniques. Size and morphological characterization are performed by Zetasizer and transmission electron microscope (TEM). For the physicochemical verification of the synergistic acid-triggered degradation induced by acetal and hydrazone bond degradation, Infrared spectroscopy and particle size measurements are used. Drug release studies show that DOX release is accelerated at acidic pH. DOX-conjugated HER2-specific peptide-carrying nanocarriers significantly enhance cytotoxicity toward SKBR-3 cells. More importantly, no selectivity toward MCF-10A cells is observed compared to HER2(+) SKBR-3 cells. Formulations cause apoptosis depending on Bax and Caspase-3 and cell cycle arrest in G2 phase. This study shows a novel system for HER2-targeted therapy of breast cancer with a multifunctional nanocarrier, which has higher stability, dual pH-sensitivity, selectivity, and it can be an efficient way of targeted anticancer drug delivery. © 2021 Wiley-VCH GmbH