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    Anticancer activity of curcumin-loaded nanocarriers: A focus on combined therapeutic modalities
    (Elsevier B.V., 2025) Senturk, Fatih; Yasar, Huriye; Bahadir, Anzel; Çakmak, Soner
    Curcumin (CUR) is a polyphenolic compound known for its various therapeutic effects, including antioxidant, antiinflammatory, and anticancer activities. Researchers have elucidated several molecular and cellular pathways through which CUR exhibits potent anticancer activity, rendering it a promising candidate for cancer therapy. The activity of CUR is attributed to three reactive functional groups: the diketone moiety and two phenolic groups. Particularly, the presence of hydroxyl (OH) groups in the phenolic ring is responsible for CUR's anticancer effects. However, the therapeutic efficacy of CUR is restricted by its hydrophobic nature, rapid degradation with a short half-life, and low bioavailability. To address these challenges, researchers have developed nano-based drug carrier systems, such as nanoparticles, liposomes, and micelles, to encapsulate and deliver CUR effectively. These nanocarriers can be customized in size, chemical composition, surface charge, and functionalization to enable targeted delivery to specific sites. Also, the surface functionalities of nanocarriers can be tailored to specific targets, such as overexpressed receptors on cancer cells, leading to improved cellular uptake and therapeutic outcomes of CUR. Furthermore, integrating CUR-loaded nanocarriers with other therapeutic modalities, such as chemotherapy (CUR and chemotherapeutic agents coloaded), magnetic nanohyperthermia, photodynamic therapy, and nanocarrier-based ultrasound therapy, holds promise for enhancing treatment efficacy. This chapter provides an extensive overview of the molecular pathways and underlying mechanisms responsible for the substantial anticancer activity of CUR. In addition, it highlights the utilization of CUR-loaded nanocarriers in combination with other therapeutic modalities to achieve enhanced efficacy in cancer therapy. The combination of CUR with other modalities has demonstrated promising results in preclinical studies, indicating the potential for a synergistic effect. © 2025 Elsevier B.V., All rights reserved.
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    Effects of radiofrequency exposure on in vitro blood-brain barrier permeability in the presence of magnetic nanoparticles
    (Academic Press Inc Elsevier Science, 2022) Şentürk, Fatih; Çakmak, Soner; Koçum, İsmail Cengiz; Gümüşderelioğlu, Menemse; Öztürk, Göknur Güler
    The blood-brain barrier (BBB) remains a major obstacle for the delivery of drugs in the treatment of many neurological diseases. In this study, we aimed to investigate the effects of radiofrequency electromagnetic fields (RF-EMFs) on the permeability of an in vitro BBB model under RF exposure alone, or in the presence of nanoparticles (NPs). For this purpose, an in vitro BBB model was established by seeding human umbilical vein endothelial cells (HUVECs) and human glioblastoma cell line (T98G) on the apical and basolateral sides of the transwell membrane, respectively. The integrity of the BBB model was confirmed by measuring transendothelial electrical resistance (TEER), and a fluorescein isothiocyanate (FITC)-dextran permeability assay was performed when the resistance reached 120 U cm(2). After the RFfield exposure (13.56 MHz, 80 W, 10 min), we found that FITC-dextran transported across the in vitro BBB was increased 10-fold compared to FITC-dextran transported without an RF-field. This notable phenomenon, which can be called the burst permeability RF effect (BP-RF), has been proposed for the first time in the literature. Subsequently, the effect of the RF-field on BBB permeability was also investigated in the presence of superparamagnetic iron oxide nanoparticles (SPIONs) and magnetic poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-b-PEG) nanoparticles (m-PNPs). It was found that the amount of both transported NPs on the basolateral sides increased after exposure to the RF-field. As a result, the RFfield can be applied simultaneously during treatment with clinical agents or nanocarriers, improving the permeability of the BBB, which may contribute to therapeutic efficacy of many drugs that are used in neurological diseases. (c) 2022 Elsevier Inc. All rights reserved.
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    Hydrolytic instability and low-loading levels of temozolomide to magnetic PLGA nanoparticles remain challenging against glioblastoma therapy
    (Elsevier, 2022) Şentürk, Fatih; Çakmak, Soner; Gümüşderelioğlu, Menemse; Öztürk, Göknur Güler
    Temozolomide (TMZ) is the first-line chemotherapeutic agent for the treatment of newly diagnosed glioblastoma (GBM). However, chemoresistance, hydrolytic instability, and insufficient drug accumulation are major challenges limiting the effectiveness of TMZ chemotherapy. Although various nanocarriers have been offered to overcome these limitations, there are some discrepancies regarding the TMZ encapsulation efficiency (EE%). In this study, by examining the behavior of TMZ in different solvents, we aimed to confirm the loading efficiency of TMZ in the nanoparticles (NPs) and investigate the therapeutic efficacy of TMZ-loaded NPs in human GBM cell line (T98G). For this purpose, firstly, we investigated the stability of TMZ and its degradation product (AIC) to evaluate whether TMZ degradation affects the measured EE% from the supernatant (indirect method) or the NPs (direct method). Subsequently, we tried to load TMZ into magnetic poly (lactic-co-glycolic acid)-polyethylene glycol (PLGA-b-PEG) nanoparticles (TMZ-m-PNPs) by modifying the synthesis parameters in a controlled manner. It was concluded that the indirect method might cause misleading results due to the high hydrolytic instability of TMZ during the NPs synthesis or washing steps. Although many modifications have been performed in the synthesis method, the EE% of TMZ ranged between 1% and 7%. In cell culture, IC50 values of free-TMZ were found for human endothelial cells (HUVEC, similar to 500 mu M) and human glioblastoma cells (T98G, similar to 350 mu M) at the 72nd h. Furthermore, cell viability was quantified using MTT, live/dead cell viability, and Annexin V-FITC/PI assays of TMZ-m-PNPs, but cytotoxicity of NPs was not dose-dependent in T98G cells. Overall, this study offers two major new insights; first, the EE% of TMZ in NPs should be determined by the direct method; second, to increase the therapeutic efficacy of TMZ-loaded NPs on GBM cells, it may be recommended not to use the PLGA-based nanocarrier system that may contribute to poor therapeutic response.