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    Fabrication of curcumin-loaded magnetic PEGylated-PLGA nanocarriers tagged with GRGDS peptide for improving anticancer activity
    (Elsevier, 2023) Senturk, Fatih; Cakmak, Soner
    Carrier-mediated drug delivery systems are highly promising as a treatment option for the targeted delivery of potent cytotoxic drugs with increased efficacy and safety. Considering that poly (lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG) polymers each provide certain advantages for biological purposes, PEGylated-PLGA nanoparticles have emerged as a leading candidate among other alternatives. Furthermore, these nanoparticles can be modified with the specific short peptide sequences such as glycine-arginine-glycine-aspartic acid -serine (GRGDS), which selectively binds to integrins overexpressed in most cancer cells, allowing for targeted delivery. Here, we reported the details in fabrication and characterization of magnetic PEGylated-PLGA nanoparticles functionalized with GRGDS peptide. In addition, superparamagnetic iron oxide nanoparticles (SPIONs) and the natural pharmaceutical compound curcumin (Cur) were loaded into these polymeric nanoparticles to assess their anticancer activity potential. Overall, this study provides comprehensive methodologies, including all synthesis procedures, challenges, and useful suggestions for peptide-conjugated polymeric nanoparticles that may be used for cellular targeting and therapeutic applications.& BULL; Step by step fabrication protocol for the Cur loaded magnetic PEGylated-PLGA nanoparticles was presented.& BULL; Validation of the fabrication and the GRGDS conjugation to the nanoparticles were shown via detailed characterization studies.& BULL; The cytotoxic effect of the Cur-loaded and GRGDS-tagged magnetic nanoparticles was tested on T98G glioblastoma cell line as a preliminary in vitro study.
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    GRGDS-conjugated and curcumin-loaded magnetic polymeric nanoparticles for the hyperthermia treatment of glioblastoma cells
    (Elsevier, 2021) Senturk, Fatih; Cakmak, Soner; Kocum, Ismail Cengiz; Gumusderelioglu, Menemse; Ozturk, Goknur Guler
    Thermally responsive and ligand-mediated drug delivery systems have the potential to improve the treatment of brain tumors, especially, most lethal one, glioblastoma multiform (GBM). Magnetic nanoparticle-mediated hyperthermia becomes one of the most promising alternative therapy for GBM treatment in cases where localized heating and targeted delivery of a therapeutic drug can be achieved on the tumor site. In this study, it is aimed to increase the therapeutic efficiency of multi-functionalized nanoparticles (NPs) in combination with radiofrequency hyperthermia (RF-HT) on GBM cells. For this purpose, firstly, a low-cost and portable home-built RFHT system suitable for in vitro/in vivo studies was successfully implemented and tested at 13.56 MHz frequency with power up to approximately 400 W. Subsequently, the highly monodispersed superparamagnetic iron oxide nanoparticles (SPIONs), which could interact with the RF magnetic field, were synthesized with the mean particle size of 5.6 +/- 0.9 nm. The obtained SPIONs were coated with poly (lactic-co-glycolic acid)-poly (ethylene glycol) di-block copolymer (PLGA-b-PEG). Most of the SPIONs were uniformly distributed in such a well-defined spherical-shaped polymeric NP. Moreover, curcumin (Cur), a potential agent for GBM treatment, was loaded into the magnetic polymeric nanoparticles (m-PNPs) with a loading capacity of 8% (w/w, Cur/NPs) and a mean diameter of Cur-loaded m-PNPs (Cur-m-PNPs) was 142 +/- 70 nm. To increase cellular uptake and targeting ability of NPs, glycine-arginine-glycine-aspartic acid-serine (GRGDS) peptide was immobilized on the Cur-m-PNPs and the amount of GRGDS was detected as 37 mu g/mg NPs. In vitro cytotoxicity studies revealed that the presence of GRGDS on Cur-m-PNPs (GRGDS-Cur-m-PNPs) improved the cytotoxic efficiency of Cur-m-PNPs by 6-fold in GBM-cells for all incubation times (24, 48 and 72 h). Furthermore, NPs with RF treatment exhibited higher antitumor activity than that of NPs without RF on GBM cells. This result may be attributed to the thermal (SPIONs) or non thermal (cellular membrane) effects or both of them on cells. Overall, this study showed that RF-HT in combination with GRGDS-Cur-m-PNPs could provide a feasible approach to improve GBM treatment.