PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Application of 3D Cell Culture Techniques in Nanotoxicology: How Far Are We(Springer, 2026) Shakeri, Raheleh; Mirjalili, Seyedeh Zohreh; Karakus, Ceyda Oksel; Safavi, MalihehInvestigation of toxicological profile and possible side effects of engineered nanomaterials (ENMs) is of high importance. Historically, two-dimensional (2D) cell culture was used to study the toxicity of the ENMs, but due to their inability to simulate in vivo cell behavior, three-dimensional (3D) cell culture systems have been developed. Nanotoxicity studies initiate with in vitro experiments and continue with in vivo studies, which are very challenging and sometimes accompanied by conflicting data due to the in vitro-in vivo gap. Thus, scientists are turning their attention to microfabrication techniques and engineered systems "called organ-on-a-chips", which act as an intermediate between in vivo and in vitro systems. The present account tries to review the classical study models and suitably cover the emerging 3D culture models including scaffold-free and scaffold-based 3D cell cultures, 3D co-culture with direct contact and without cell-cell contact methods as well as microfluidic-based tissue chips and organoids. Overall, this review aims to give readers a better insight about the ENMs' toxicology and fill the gaps between the knowledge and practical techniques. Hopefully, the presented information will resolve the issues of 2D in vitro cultures and display the clinically relevant responses to the concerns of therapeutic ENMs.Article Liposomal Encapsulation of a Synthetic Bromophenol for Antitumor Efficacy and Apoptotic Activity in Cancer Cells(Springer, 2026) Oztanrikulu, Bercem Dilan; Ozdemir, Ekrem; Avci, Bahri; Goksu, Suleyman; Bayrakceken, Handan Uguz; Askin, HakanA novel synthetic bromophenol (BP), inspired by marine-derived natural bromophenols, was evaluated for its antitumor activity and for the enhancement of its in vitro performance through liposomal encapsulation (LipoBP). Etoposide was used as a reference in characterization, release, and loading studies. PEGylated liposomes were employed to improve BP's solubility, bioavailability, and therapeutic potential. The cytotoxicity, apoptosis, and gene expression effects of free BP and LipoBP were assessed in A549 (lung) and MCF-7 (breast) cancer cell lines. WST-8 assays showed that encapsulation significantly increased BP's cytotoxic activity, particularly in A549 cells, while flow cytometry and Annexin V-FITC/PI analyses indicated more pronounced apoptotic induction by LipoBP compared with free BP. qRT-PCR analyses revealed upregulation of proapoptotic genes (BAX, CASP6, CASP3 and CASP9) and downregulation of antiapoptotic/survival genes (BCL-XL, IQSEC2) in both cell lines, indicating activation of intrinsic apoptotic pathways. Plain liposomes exhibited minimal cytotoxicity, confirming their biocompatibility. Liposomal bromophenol, which we have introduced to the literature for the first time, is expected to be a promising nanocarrier system that could be effective in cancer treatment by improving the therapeutic index of new drug candidates such as marine bromophenols.Article Citation - WoS: 1Citation - Scopus: 1Shape and Surface Modification Dependent Cellular Interactions of Gold Nanoparticles in a 3D Blood-Brain Supported Neurospheroid Model(Churchill Livingstone, 2025) Tomak, Aysel; Saglam-Metiner, Pelin; Coban, Reyhan; Oksel-Karakus, Ceyda; Yesil-Celiktas, OzlemRecent investigations have begun to explore the cellular interactions of nanoparticles (NPs) in three-dimensional (3D) neuro-spheroid models of the blood-brain barrier (BBB), offering novel insights into NP transport across the barrier and their potential neurotoxic effects. Building on these findings, we investigated the effects of particle shape and surface modification on the transport dynamics and cellular interactions of gold NPs (AuNPs) using a multicellular 3D spheroid model of the BBB. AuNPs with two different morphologies, spherical and rod-like, were synthesized, modified with polyethylene glycol (PEG) and characterized in detail using Ultraviolet-Visible (UV-Vis) Spectroscopy, Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS) techniques. A 3D neuro-spheroid model consisting of mouse brain endothelial cells (bEnd.3), motor neuron-like hybrid cells (NSC-34) and glial cells (C6) was employed to evaluate the BBB transport characteristics and cytotoxicity of bare and PEG-coated spherical and rod-shaped AuNPs. Our results indicated that 3D neurospheroid models can serve as orchestral platforms for studying cellular behaviour of NPs. PEGylation of NPs substantially reduced cytotoxic effects compared to bare particles. While spherical AuNPs showed limited translocation through the endothelial barrier, those that entered the spheroid were found to be distributed deeper within the interior. In contrast, rod-shaped particles exhibited a greater capacity to cross the BBB but tended to accumulate near the periphery without deeper penetration. These findings underscore the critical role of shape and surface chemistry in nanoparticle-mediated BBB transport and support the utility of 3D neuro-spheroid models in predicting nanoparticle behavior in brain tissue.Review Citation - WoS: 69Nanoparticle-Protein Corona Complex: Understanding Multiple Interactions Between Environmental Factors, Corona Formation, and Biological Activity(TAYLOR & FRANCIS LTD, 2021) Tomak, Aysel; Tomak, Aysel; Çesmeli, Selin; Öksel Karakuş, Ceyda; Hanoglu, Bercem D.; Winkler, David; Oksel Karakus, CeydaThe surfaces of pristine nanoparticles become rapidly coated by proteins in biological fluids, forming the so-called protein corona. The corona modifies key physicochemical characteristics of nanoparticle surfaces that modulate its biological and pharmacokinetic activity, biodistribution, and safety. In the two decades since the protein corona was identified, the importance of nanoparticles surface properties in regulating biological responses have been recognized. However, there is still a lack of clarity about the relationships between physiological conditions and corona composition over time, and how this controls biological activities/interactions. Here we review recent progress in characterizing the structure and composition of protein corona as a function of biological fluid and time. We summarize the influence of nanoparticle characteristics on protein corona composition and discuss the relevance of protein corona to the biological activity and fate of nanoparticles. The aim is to provide a critical summary of the key factors that affect protein corona formation (e.g. characteristics of nanoparticles and biological environment) and how the corona modulates biological activity, cellular uptake, biodistribution, and drug delivery. In addition to a discussion on the importance of the characterization of protein corona adsorbed on nanoparticle surfaces under conditions that mimic relevant physiological environment, we discuss the unresolved technical issues related to the characterization of nanoparticle-protein corona complexes during their journey in the body. Lastly, the paper offers a perspective on how the existing nanomaterial toxicity data obtained from in vitro studies should be reconsidered in the light of the presence of a protein corona, and how recent advances in fields, such as proteomics and machine learning can be integrated into the quantitative analysis of protein corona components.