Research Project: PEI Kaplı Yakın-Kızılötesi Bölgede Işıyan Biyouyumlu Ag2S Kuantum Nokyacıklarının Sentezlenmesi ve Transfeksiyon Vektörü Olarak Değe rlendirilmesi
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Contributors
Funders
ID
TB.00165
Authors
Acar, Havva Funda Yağcı
Faculty Member
Publications
Etoposide loaded SPION-PNIPAM nanoparticles improve thein vitrotherapeutic outcome on metastatic prostate cancer cells via enhanced apoptosis
(Wiley-V C H Verlag , 2020) Acar, Havva Funda Yağcı; Khodadust, Rouhollah; Ülkü, İrem; Yar, Yasemin; Erkısa, Merve; Arı, Ferda; Ulukaya, Engin; Department of Chemistry; Graduate School of Sciences and Engineering; Yes; College of Sciences; GRADUATE SCHOOL OF SCIENCES AND ENGINEERING
Prostate cancer is among the leading causes of death worldwide because its metastatic form is a deadly disease. Therefore, the development of new chemotherapeutics is of immense importance. Nanoparticle technology seems to provide diverse options in this regard. Therefore, poly(N-isopropylacrylamide) (PNIPAM) coated superparamagnetic iron oxide nanoparticles (SPION) loaded with Etoposide were prepared in small sizes (57 nm) and with 3.5 % drug content to improve the efficiency of Etoposide in prostate cancer therapy. Sustained release of the drug was achieved, which found to be sensitive to low pH and high temperature. The anti-growth activity of SPION-PNIPAM-Etoposide formulation against metastatic prostate cancer cells (PC-3, LNCaP) were investigated by SRB assay, then, confirmed by ATP assay. Mode of cell death was evaluated by using flow cytometry analyses. A significant improvement of nanoformulated drug was observed at 5-10 mu g/ml doses of the drug in both cell lines. More importantly, this formulation enhanced the cytotoxic effect of Etoposide on PC-3 cells, which is considered more resistant to Etoposide than LNCaP and reduced the IC(50)value by 55 % reaching to 4.5 mu g drug/ml, which is a very significant improvement in the literature. It was clearly shown that nanoformulated drug provided about 3-fold increases in caspase-dependent early apoptotic cells in PC-3 cells. The novel formulation seems to successfully cause cell death of especially PC-3 metastatic prostate cancer cells. It should therefore be taken into consideration for further animal studies as a novel potent anticancer agent.
Bypassing pro-survival and resistance mechanisms of autophagy in EGFR-positive lung cancer cells by targeted delivery of 5FU using theranostic Ag2S quantum dots
(Royal Society of Chemistry, 2019) Acar, Havva Funda Yağcı; Bavili, Nima; Demirci, Gözde; Duman, Fatma Demir; Kiraz, Alper; Akkoç, Yunus; Gözüaçık, Devrim; Department of Chemistry; Department of Physics; School of Medicine; KUYTAM (Koç University Surface Science and Technology Center); Yes; College of Sciences; SCHOOL OF MEDICINE; Research Center
Targeted drug delivery systems that combine imaging and therapeutic functions in a single structure have become very popular in nanomedicine. Near-infrared (NIR) emitting Ag2S quantum dots (QDs) are excellent candidates for this task. Here, we have developed PEGylated Ag2S QDs functionalized with Cetuximab (Cet) antibody and loaded with an anticancer drug, 5-fluorouracil (5FU). These theranostic QDs were used for targeted NIR imaging and treatment of lung cancer using low (H1299) and high (A549) Epidermal Growth Factor Receptor (EGFR) overexpressing cell lines. The Cet conjugated QDs effectively and selectively delivered 5FU to A549 cells and provided significantly enhanced cell death associated with apoptosis. Interestingly, while treatment of cells with free 5FU activated autophagy, a cellular mechanism conferring resistance to cell death, these EGFR targeting multimodal QDs significantly overcame drug resistance compared to 5FU treatment alone. The improved therapeutic outcome of 5FU delivered to A549 cells by Cet conjugated Ag2S QDs is suggested as the synergistic outcome of enhanced receptor mediated uptake of nanoparticles, and hence the drug, coupled with suppressed autophagy even in the absence of addition of an autophagy suppressor.
