Erkan GUMUS, Ayca TAS, Yavuz SİLİG, Neşe KEKLİKCİOĞLU ÇAKMAK, Mustafa ATABEY

Chemotherapeutic effects of doxorubicin loaded PEG coated TiO? nanocarriers on breast cancer cell lines

Aim: Breast cancer is the most common frequently diagnosed malignancy among women and leading cause of cancer death inwomen worldwide. The aim of this study is 1) to increase the biocompatibility of the titanium dioxide (TiO?) nanoparticles (NPs)by coating it with PolyEthylene Glycol (PEG) and to develop a new nanostructure system and 2) to determine anticancer activity ofdoxorubicin (DOX) loaded PEG-TiO? on MDA-MB-231 cell lines.Material and Methods: TiO? nanoparticles used in this study were synthesized, coated with PEG, and PEG-TiO? nanostructure systemwas loaded by DOX. UV analysis was performed on the prepared solutions. The synthesized drugs were applied to the MDA-MB-231breast cancer cell line and cytotoxic effect of these drugs were determined by using MTT method. The MDA-MB-231 cells weretreated with different concentrations of TiO? (5-100 μg/ml) for 24, 48 and 72 hours. Apoptosis and necrosis were determined byfluorescence microscopy using the Hoechst 33258 (HO) /propidium iodide (PI) double staining.Results: The effects of TiO?, PEG-TiO?, DOX, and TiO?-PEG-DOX on the MDA-MB-231 cell line were compared with the control groupand IC50 values were determined for 24, 48 and 72 hours.Conclusion: In this study, it was shown that the effect of TiO?-PEG-DOX nanostructured system on MDA-MB-231 cell line wasinhibition growth in cancer cells and induction of apoptosis when compared with control group and DOX.

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1. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA: a cancer journal for clinicians 2011;61:69-90.
2. Marsh S, McLeod HL. Pharmacogenetics and oncology treatment for breast cancer. Expert opinion on pharmacotherapy 2007;8:119-27.
3. Youlden DR, Cramb SM, Dunn NA, et al. The descriptive epidemiology of female breast cancer: an international comparison of screening, incidence, survival and mortality. Cancer epidemiology 2012;36:237-48.
4. Singh R, Lillard JW Jr. Nanoparticle-based targeted drug delivery. Exp Mol Pathol 2009;86:215-23.
5. Tan B, Piwnica-Worms D, Ratner L. Multidrug resistance transporters and modulation. Curr opin oncol 2000;12:450- 8.
6. Mayer LD, Shabbits JA. The role for liposomal drug delivery in molecular and pharmacological strategies to overcome multidrug resistance. Cancer Metastasis Rev 2001;20:87- 93.
7. Coley HM. Mechanisms and strategies to overcome chemotherapy resistance in metastatic breast cancer. Cancer Treat Rev 2008;34:378-90.
8. Schöndorf T, Kurbacher CM, Göhring UJ, et al. Induction of MDR1-gene expression by antineoplastic agents in ovarian cancer cell lines. Anticancer Res 2002;22:2199-203.
9. Linn SC, Giaccone G. Mdr1/P-Glycoprotein expression in colorectal-cancer. Eur J Cancer 1995;31:1291-4.
10. Yu ST, Chen TM, Tseng SY, et al. Tryptanthrin inhibits MDR1 and reverses doxorubicin resistance in breast cancer cells. Biochem Biophys Res Comm 2007;358:79-84.
11. Minotti G, Menna P, Salvatorelli E, et al. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev 2004;56:185-229.
12. Patil RR, Guhagarkar SA, Devarajan PV. Engineered nanocarriers of doxorubicin: a current update. Crit Rev Ther Drug Carrier Syst 2008;25:1-61.
13. Peer D, Karp J M, Hong S, et al. Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2007;2:751- 60.
14. Jabr-Milane LS, van Vlerken LE, Yadav S, et al. Multifunctional nanocarriers to overcome tumor drug resistance. Cancer Treat Rev 2008;34:592-602.
15. Cho K, Wang XU, Nie S, et al. Therapeutic nanoparticles for drug delivery in cancer. Clin Cancer Res 2008;14:1310-6.
16. Venkatasubbu D, Ramasamy S, Ramakrishnan V, et al. Folate targeted PEGylated titanium dioxide nanoparticles as a nanocarrier for targeted paclitaxel drug delivery. Advan Powder Technol 2013;24:947-54.
17. Chen Y, Wan Y, Wang Y, et al. Anticancer efficacy enhancement and attenuation of side effects of doxorubicin with titanium dioxide nanoparticles. Int J Nanomedicine 2011;6:2321.
18. Li Q, Wang X, Lu X, et al. The incorporation of daunorubicin in cancer cells through the use of titanium dioxide whiskers Biomaterial 2009;30:4708-15.
19. Lopez T, Sotelo J, Navarrete J, et al. Synthesis of TiO? nanostructured reservoir with temozolomide: Structural evolution of the occluded drug. Optical Materials 2006;29:88-94.
20. Kim C, Kim S, Oh W, et al. Efficient intracellular delivery of camptothecin by silica/titania hollow nanoparticles. Chemistry–A Eur J 2012;18:4902-08.
21. Yin ZF, Wu L, Yang HG. et al. Recent progress in biomedical applications of titanium dioxide. Phys. Chem Chem Phys 2013;15:4844-58.
22. Qin Y, Sun L, Li X, et al. Highly water-dispersible TiO2 nanoparticles for doxorubicin delivery: Effect of loading mode on therapeutic efficacy. J Material Chemistry 2011;21:18003-10.
23. Wu KC, Yamauchi Y, Hong CY, et al. Biocompatible, surface functionalized mesoporous titania nanoparticles for intracellular imaging and anticancer drug delivery. Chem Commun 2011;47:5232-4.
24. Yamaguchi S, Kobayashi H, Narita T, et al. Novel photodynamic therapy using water-dispersed TiO?– polyethylene glycol compound: evaluation of antitumor effect on glioma cells and spheroids in vitro. Photochem Photobiol 2010;86:964-71.
25. Wang M, Xie F, Wen X, et al. Therapeutic PEG-ceramide nanomicelles synergize with salinomycin to target both liver cancer cells and cancer stem cells. Nanomedicine 2017;12: 1025-42.
26. Yao XL, Yoshioka Y, Ruan GX, et al. Optimization and internalization mechanisms of PEGylated adenovirus vector with targeting peptide for cancer gene therapy. Biomacromolecules 2012;13:2402-9.
27. Balalaeva IV, Zdobnova TA, Krutova IV, et al. Passive and active targeting of quantum dots for whole-body fluorescence imaging of breast cancer xenografts. J Biophotonisc 2012;5:860-7.
28. Sykes E. A, Chen J, Zheng G, et al. Investigating the impact of nanoparticle size on active and passive tumor targeting efficiency. ACS nano 2014;8:5696-706.
29. Mahbubul I. M, Elcioglu EB, Saidur R, et al. Optimization of ultrasonication period for better dispersion and stability of TiO?–water nanofluid. Ultrason Sonochem 2017;37:360-7.
30. Du Yu, Ren W, Li Y, et al. The enhanced chemotherapeutic effects of doxorubicin loaded PEG coated TiO2 nanocarriers in an orthotopic breast tumor bearing mouse model. J Material Chemist B 2015;3:1518-28.
31. Skehan P, Storeng R, Scudiero D, et al. New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst 1990;82:1107-12.
32. Syed Abdul Rahman SN, Abdul Wahab N, Abd Malek SN. In vitro morphological assessment of apoptosis induced by antiproliferative constituents from the rhizomes of Curcuma zedoaria. Evid-Based Complementary Alternat Med 2013;2013:257108.
33. Ren W, Zeng L, Shen Z, et al. Enhanced doxorubicin transport to multidrug resistant breast cancer cells via TiO2 nanocarriers. RSC Advances 2013;43:20855-61.
34. Perrault SD, Walkey C, Jennings T, et al. Mediating tumor targeting efficiency of nanoparticles through design. Nano lett 2009;9:1909-15.
35. Shi Y, Wang F, He J, et al. Titanium dioxide nanoparticles cause apoptosis in BEAS-2B cells through the caspase 8/t-Bid-independent mitochondrial pathway. Toxicol lett 2010;196:21-7.
36. Nasr R, Hasanzadeh H, Khaleghian A, et al. Induction of apoptosis and inhibition of invasion in gastric cancer cells by titanium dioxide nanoparticles. Oman Med 2018;33:111- 7.
37. Rezaei-Tavirani M, Dolat E, Hasanzadeh H, et al. TiO2 nanoparticle as a sensitizer drug in radiotherapy: in vitro study. Iranian J Cancer Prevent 2013;6:37-44.
38. Thurn KT, Arora H, Paunesku T, et al. Endocytosis of titanium dioxide nanoparticles in prostate cancer PC-3M cells. Nanomedicine 2011;7:123-30.