Research Article


DOI :10.26650/IUITFD.1567946   IUP :10.26650/IUITFD.1567946    Full Text (PDF)

SYNTHESIS, CHARACTERISATION, AND INVESTIGATION OF THE ANTICANCER POTENTIAL OF CARMOFUR-LOADED SILVER NANOPARTICLES

Ferdane Danışman Kalındemirtaşİshak Afşin KariperDilşad ÖzerkanDürdane Serap Kuruca

Objective: The term "triple-negative breast cancer" (TNBC) is used to describe tumours that do not express oestrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2). TNBC tends to be more aggressive than other types of breast cancer. Current antineoplastic drugs have limited treatment options for malignant breast cancer owing to their narrow therapeutic index, toxicity, resistance, and nonselectivity. Therefore, there is a need for the prompt development of new medicinal drugs for TNBC. Here, we investigated the growth inhibition potential of carmofur-bonded silver nanoparticles (AgNPs-Car) on two TNBC cell lines, MDA-MB-231 and 4T1, and compared the effects with non-cancerous Human umbilical vein endothelial cells (HUVECs).

Material and Methods: AgNPs-Car were synthesised and characterisedby FTIR, DLS, SEM, and EDX. The anticancer effect was evaluated using a 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay.

Results: AgNPs-Car was determined to be predominantly more effective than Car alone. Mainly, 4T1 cells were 5.7-fold more sensitive to AgNPs-Car than Car alone. While AgNPs showed no considerable toxicity on HUVECs, they significantly induced the cytotoxicity of MDA-MB-231 and 4T1 cells.

Conclusion: Our results showed that AgNPs-Car is a promising anticancer agent due to its highly potent and selective growth inhibitory effect on TNBC cells.

DOI :10.26650/IUITFD.1567946   IUP :10.26650/IUITFD.1567946    Full Text (PDF)

KARMOFUR YÜKLÜ GÜMÜŞ NANOPARTİKÜLLERİNİN SENTEZİ, KARAKTERİZASYONU VE ANTİKANSER POTANSİYELİNİN ARAŞTIRILMASI

Ferdane Danışman Kalındemirtaşİshak Afşin KariperDilşad ÖzerkanDürdane Serap Kuruca

Amaç: "Üçlü negatif meme kanseri" (TNBC) terimi, östrojen reseptörü (ER), progesteron reseptörü (PR) veya insan epidermal büyüme faktörü reseptörü 2'yi (HER2) eksprese etmeyen tümörleri tanımlamak için kullanılır. TNBC, diğer meme kanseri türlerinden daha agresif olma eğilimindedir. Malign meme kanserinde güncel antineoplastik ilaçların tedavi indeksinin kısıtlayıcı olması, toksisitesi, direnci ve seçici olmaması nedeniyle sınırlı tedavi seçenekleri bulunmaktadır. Bu nedenle, TNBC için yeni tıbbi ilaçların derhal geliştirilmesine ihtiyaç vardır. Burada, MDA-MB-231 ve 4T1 olmak üzere iki TNBC hücre hattı üzerinde karmofur bağlı gümüş nanopartiküllerin (AgNP-Car) büyüme inhibisyonuna etkisini araştırdık ve etkinliklerini kanserli olmayan insan göbek damarı endotel hücreleri (HUVEC) ile karşılaştırdık.

Gereç ve Yöntem: AgNP-Car, FTIR, DLS, SEM ve EDX ile sentezlendi ve karakterize edildi. Anti-kanser etkisi 3-(4,5-Dimetiltiyazol- 2-il)-2,5-Difeniltetrazolium Bromür (MTT) testi ile değerlendirildi.

Bulgular: AgNP-Car'ın nanopartiküllerin tek başına karmofurdan ağırlıklı olarak daha etkili olduğu belirlendi. Özellikle AgNP-Car uygulanmış 4T1 hücrelerinin, karmofur uygulanmış gruplara göre 5,7 kat daha duyarlı olduğu belirlendi. AgNP'ler HUVEC'ler üzerinde önemli bir toksisite göstermezken; MDA-MB-231 ve 4T1 hücrelerinin sitotoksisitesini önemli ölçüde indüklediler.

Sonuç: Sonuçlarımız, AgNP-Car'ın TNBC hücreleri için oldukça güçlü ve seçici büyüme inhibitörü etkisi nedeniyle umut verici bir anti-kanser ajanı olabileceğini göstermektedir.


PDF View

References

  • Liyanage PY, Hettiarachchi SD, Zhou Y, Ouhtit A, Seven ES, Oztan C, et al. Nanoparticle-mediated targeted drug delivery for breast cancer treatment. Biochimica Et Biophysica Acta - Reviews on Cancer 2019;1871(2):419-33. [CrossRef] google scholar
  • Jamdade VS, Sethi N, Mundhe N, Kumar P, Lahkar M, Sinha N. Therapeutic targets of triple-negative breast cancer: a review. Br J Pharmacol 2015;172(17):4228-37. [CrossRef] google scholar
  • Fahmy SA, Mahdy NK, Mohamed AH, Mokhtar FA, Youness RA. Hijacking 5-fluorouracil chemoresistance in triple negative breast cancer via microRNAs-loaded chitosan nanoparticles. Int J Mol Sci 2024;25(4):2070. [CrossRef] google scholar
  • McGee SF. Understanding metastasis: Current paradigms and therapeutic challenges in breast cancer progression. RCSI Stud Med J 2010;3:56-60. google scholar
  • Dasari N, Guntuku GS, Pindiprolu SKS. Targeting triple negative breast cancer stem cells using nanocarriers. Discover Nano 2024;19(1):41. [CrossRef] google scholar
  • Nakamura Y, Mochida A, Choyke PL, Kobayashi H. Nanodrug delivery: Is the enhanced permeability and retention effect sufficient for curing cancer? Bioconjug Chem 2016;27(10):2225-38. [CrossRef] google scholar
  • Islam MM, Mirza SP. Versatile use of Carmofur: A comprehensive review of its chemistry and pharmacology. Drug Dev Res 2022;83(7):1505-18. [CrossRef] google scholar
  • Nosrati H, Hamzepoor M, Sohrabi M, Saidijam M, Assari MJ, Shabab N, et al. The potential renal toxicity of silver nanoparticles after repeated oral exposure and its underlying mechanisms. BMC Nephrology 2021;22(1):228. [CrossRef] google scholar
  • Sakamoto J, Oba K, Matsui T, Kobayashi M Efficacy of oral anticancer agents for colorectal cancer Dis Colon Rectum 2006;49:82-S91 [CrossRef] google scholar
  • Morimoto K, Koh M Postoperative adjuvant use of Carmofur for early breast cancer Osaka City Med J 2003;49(2):77-83 google scholar
  • Realini N, Solorzano C, Pagliuca C, Pizzirani D, Armirotti A, Luciani R, et al Discovery of highly potent acid ceramidase inhibitors with in vitro tumor chemosensitizing activity Sci Rep 2013;3(1):1035 [CrossRef] google scholar
  • Taniguchi M, Okazaki T Role of ceramide/sphingomyelin (SM) balance regulated through “SM cycle” in cancer Cell Signal 2020;87:110119 [CrossRef] google scholar
  • Sharma D, Czarnota GJ Involvement of ceramide signalling in Radiation-Induced tumour vascular effects and Vascular-Targeted therapy Int J Mol Sci 2022;23(12):6671 [CrossRef] google scholar
  • Dementiev A, Joachimiak A, Nguyen HS, Gorelik A, Illes K, Shabani S, et al Molecular mechanism of inhibition of acid ceramidase by Carmofur J Med Chem 2018;62(2):987-92 [CrossRef] google scholar
  • Domracheva I, Muhamadejev R, Petrova MV, Liepin’sh EE, Gulbe A, Shestakova I, et al 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) increases Carmofur stability and in vitro antiproliferative effect Toxicol Rep 2015;2:377-83 [CrossRef] google scholar
  • Saied EM, Arenz C Small molecule inhibitors of ceramidases Cellular Physiol Biochem 2014;34(1):197-212 [CrossRef] google scholar
  • Ma P, Mumper RJ Paclitaxel nano-delivery systems: A comprehensive review J Nanomed Nanotech 2013;4(2):1000164 [CrossRef] google scholar
  • Kulkarni SK Nanotechnology: Principles and practices Springer eBooks 2015; 293 https://doi org/10 1007/978-3-319-09171-6 [CrossRef] google scholar
  • Arvizo RR, Bhattacharyya S, Kudgus RA, Giri K, Bhattacharya R, Mukherjee P Intrinsic therapeutic applications of noble metal nanoparticles: past, present and future Chem Soc Rev 2012;41(7):2943 [CrossRef] google scholar
  • Dykman LA, Khlebtsov NG Gold nanoparticles in biomedical applications: recent advances and perspectives Chem Soc Rev 2012;41(6):2256-82 [CrossRef] google scholar
  • Limbach LK, Wick P, Manser P, Grass RN, Bruinink AA, Stark WJ Exposure of engineered nanoparticles to human lung epithelial cells: influence of chemical composition and catalytic activity on oxidative stress Environ Sci Tech 2007;41(11):4158-63 [CrossRef] google scholar
  • Pal S, Tak YK, Song JM Does the antibacterial activity of silver nanoparticles depend on the shape of the nanoparticle? A study of the gram-negative bacterium Escherichia coli Appl Environ Microbiol 2007;73(6):1712-20 [CrossRef] google scholar
  • Piao MJ, Kang KA, Lee IK, Kim HS, Kim S, Choi JY, et al Silver nanoparticles induce oxidative cell damage in human liver cells through inhibition of reduced glutathione and induction of mitochondria-involved apoptosis Toxicol Lett 2011;201(1):92-100 [CrossRef] google scholar
  • Gliga AR, Skoglund S, Wallinder IO, Fadeel B, Karlsson H Size-dependent cytotoxicity of silver nanoparticles in human lung cells: the role of cellular uptake, agglomeration and Ag release Part Fibre Toxicol 2014;11:1-17 [CrossRef] google scholar
  • Miethling-Graff R, Rumpker R, Richter M, Verano-Braga T, Kjeldsen F, Brewer JR, et al Exposure to silver nanoparticles induces size- and dose-dependent oxidative stress and cytotoxicity in human colon carcinoma cells Toxicol in Vitro 2014;28(7):1280-9 [CrossRef] google scholar
  • Khan AU, Yuan Q, Wei Y, Khan SU, Tahir K, Khan ZUH, et al Longan fruit juice mediated synthesis of uniformly dispersed spherical AuNPs: cytotoxicity against human breast cancer cell line MCF-7, antioxidant and fluorescent properties RSC Advances 2016;6(28):23775-82 [CrossRef] google scholar
  • Ahmad A, Wei Y, Syed F, Khan S, Khan GM, Tahir K, et al Isatis tinctoria mediated synthesis of amphotericin B-bound silver nanoparticles with enhanced photoinduced antileishmanial activity: A novel green approach J Photochem Photobiol B-biology 2016;161:17-24 [CrossRef] google scholar
  • Khatami M, Sharifi I, Nobre MAL, Zafarnia N, Aflatoonian MR Waste-grass-mediated green synthesis of silver nanoparticles and evaluation of their anticancer, antifungal and antibacterial activity Green Chem Lett Rev 2018;11(2):125-34 [CrossRef] google scholar
  • Kang DY, Sp N, Kim DH, Joung YH, Lee HG, Park YM, et al Salidroside inhibits migration, invasion and angiogenesis of MDA-MB 231 TNBC cells by regulating EGFR/Jak2/STAT3 signaling via MMP2 Int J Oncol 2018;53(2),877-85 [CrossRef] google scholar
  • Schrörs B, Boegel S,AlbrechtC, BukurT, BukurV, Holtstrater, C, et al Multi-Omics characterization of the 4T1 murine mammary gland tumor model Front Oncol 2020;10:1195 [CrossRef] google scholar
  • Kumar P, Nagarajan A, Uchil PD Analysis of cell viability by the MTT Assay CSH Protocols 2018:pdb prot095505 [CrossRef] google scholar
  • Danışman-Kalındemirtaş F, Kariper IA, Hepokur C, Erdem-Kuruca S Selective cytotoxicity of paclitaxel bonded silver nanoparticle on different cancer cells J Drug Deliver Sci Tech 2021;61:102265 [CrossRef] google scholar
  • Ferrari P, Scatena C, Ghilli M, Bargagna I, Lorenzini G, Nicolini A Molecular mechanisms, biomarkers and emerging therapies for chemotherapy resistant TNBC Int J Mol Sci 2022;23(3):1665 [CrossRef] google scholar
  • Clogston JD, Crist RM, Dobrovolskaia MA, Stern ST Characterization of nanoparticles intended for drug delivery Humana Press 2024;63-70 [CrossRef] google scholar
  • Hepokur C, Kariper IA, Misir S, Ay E, Tunoğlu S, Ersez MS, et al Silver nanoparticle/capecitabine for breast cancer cell treatment Toxicol in Vitro 2019;61:104600 [CrossRef] google scholar
  • Fissan H, Ristig S, Kaminski H, Asbach C, Epple M Comparison of different characterization methods for nanoparticle dispersions before and after aerosolization Anal Method 2014;6(18):7324 [CrossRef] google scholar
  • Ramos AP, Cruz MAE, Tovani CB, Ciancaglini P Biomedical applications of nanotechnology Biophysical Rev 2017;9(2):79-89 [CrossRef] google scholar
  • Schmidt C, Storsberg J Nanomaterials-Tools, technology and methodology of nanotechnology based biomedical systems for diagnostics and therapy Biomed 2015;3(3):203-23 [CrossRef] google scholar
  • Hare JI, Lammers T, Ashford M, Puri S, Storm G, Barry ST Challenges and strategies in anticancer nanomedicine development: An industry perspective Adv Drug Deliv Rev 2017;108:25-38 [CrossRef] google scholar
  • Jahan ST, Sadat SMA, Walliser M, Haddadi A Targeted therapeutic nanoparticles: An immense promise to fight against cancer J Drug Deliv 2017(1):9090325 [CrossRef] google scholar
  • Jurj A, Braicu C, Pop L, Tomuleasa C, Gherman C, Berindan-Neagoe I. The new era of nanotechnology, an alternative to change cancer treatment. Drug Des Devel Ther 2017:11:2871-90. [CrossRef] google scholar
  • Ivanova NA, Gugleva V, Dobreva M, Ivaylo P, Stefanov S, Andonova V. Silver nanoparticles as Multi-Functional Drug Delivery Systems. IntechOpen eBooks. 2019; pp. 71-92 London, UK. https://doi.org/10.5772/intechopen.80238. [CrossRef] google scholar
  • Shelton JR, Lu X, Hollenbaugh JA, Cho JH, Amblard F, Schinazi RF. Metabolism, biochemical actions, and chemical synthesis of anticancer nucleosides, nucleotides, and base analogs. Chem Rev 2016;116(23):14379-455. [CrossRef] google scholar
  • Swanner J, Fahrenholtz CD, Tenvooren I, Bernish BW, Sears JJ, Hooker A, et al. Silver nanoparticles selectively treat triple-negative breast cancer cells without affecting non-malignant breast epithelial cells in vitro and in vivo. FASEB bioAdvances 2019;1(10):639-60. [CrossRef] google scholar
  • Tominaga T, Kimura M, Asaga T, Yoshida M, Awane H, Koyama H, et al. 1-Hexylcarbamoyl-5-fluorouracil + cyclophosphamide + tamoxifen versus CMF + tamoxifen in women with lymph node-positive breast cancer after primary surgery: A randomized controlled trial. Oncol Rep 2004;12(4):797-803. [CrossRef] google scholar
  • Doan N, Nguyen HS, Montoure A, Al-Gizawiy MM, Mueller WM, Kurpad S, et al. Acid ceramidase is a novel drug target for pediatric brain tumors. Oncotar 2017;8(15):24753-61. [CrossRef] google scholar
  • Gu T, Lu A, Wang X, Brahan N, Xu L, Zhang L, et al. Synthesis and evaluation of carmofur analogs as antiproliferative agents, inhibitors to the main protease (Mpro) of SARS-CoV-2, and membrane rupture-inducing agents. bioRxiv 2024;2024-10. [CrossRef] google scholar
  • Obeid LM, Hannun YA. Ceramide: a stress signal and mediator of growth suppression and apoptosis. J Cell Biochem 1995;58:191-8. [CrossRef] google scholar
  • Reddi KK, Chava S, Chabattula SC, Edwards YJ, Singh K, Gupta R. ASAH1 facilitates TNBC by DUSP5 suppression-driven activation of MAP kinase pathway and represents a therapeutic vulnerability. Cell Death Dis 2024;15(6):452. [CrossRef] google scholar
  • Çömlekçi E, Kutlu HM, Sezer CV. Toward stimulating apoptosis in human lung adenocarcinoma cells by novel nano-carmofur compound treatment. Anticancer Drug 2018;32(6):657-63. [CrossRef] google scholar

Citations

Copy and paste a formatted citation or use one of the options to export in your chosen format


EXPORT



APA

Danışman Kalındemirtaş, F., Kariper, İ.A., Özerkan, D., & Kuruca, D.S. (2025). SYNTHESIS, CHARACTERISATION, AND INVESTIGATION OF THE ANTICANCER POTENTIAL OF CARMOFUR-LOADED SILVER NANOPARTICLES. Journal of Istanbul Faculty of Medicine, 88(2), 118-127. https://doi.org/10.26650/IUITFD.1567946


AMA

Danışman Kalındemirtaş F, Kariper İ A, Özerkan D, Kuruca D S. SYNTHESIS, CHARACTERISATION, AND INVESTIGATION OF THE ANTICANCER POTENTIAL OF CARMOFUR-LOADED SILVER NANOPARTICLES. Journal of Istanbul Faculty of Medicine. 2025;88(2):118-127. https://doi.org/10.26650/IUITFD.1567946


ABNT

Danışman Kalındemirtaş, F.; Kariper, İ.A.; Özerkan, D.; Kuruca, D.S. SYNTHESIS, CHARACTERISATION, AND INVESTIGATION OF THE ANTICANCER POTENTIAL OF CARMOFUR-LOADED SILVER NANOPARTICLES. Journal of Istanbul Faculty of Medicine, [Publisher Location], v. 88, n. 2, p. 118-127, 2025.


Chicago: Author-Date Style

Danışman Kalındemirtaş, Ferdane, and İshak Afşin Kariper and Dilşad Özerkan and Dürdane Serap Kuruca. 2025. “SYNTHESIS, CHARACTERISATION, AND INVESTIGATION OF THE ANTICANCER POTENTIAL OF CARMOFUR-LOADED SILVER NANOPARTICLES.” Journal of Istanbul Faculty of Medicine 88, no. 2: 118-127. https://doi.org/10.26650/IUITFD.1567946


Chicago: Humanities Style

Danışman Kalındemirtaş, Ferdane, and İshak Afşin Kariper and Dilşad Özerkan and Dürdane Serap Kuruca. SYNTHESIS, CHARACTERISATION, AND INVESTIGATION OF THE ANTICANCER POTENTIAL OF CARMOFUR-LOADED SILVER NANOPARTICLES.” Journal of Istanbul Faculty of Medicine 88, no. 2 (Jun. 2025): 118-127. https://doi.org/10.26650/IUITFD.1567946


Harvard: Australian Style

Danışman Kalındemirtaş, F & Kariper, İA & Özerkan, D & Kuruca, DS 2025, 'SYNTHESIS, CHARACTERISATION, AND INVESTIGATION OF THE ANTICANCER POTENTIAL OF CARMOFUR-LOADED SILVER NANOPARTICLES', Journal of Istanbul Faculty of Medicine, vol. 88, no. 2, pp. 118-127, viewed 26 Jun. 2025, https://doi.org/10.26650/IUITFD.1567946


Harvard: Author-Date Style

Danışman Kalındemirtaş, F. and Kariper, İ.A. and Özerkan, D. and Kuruca, D.S. (2025) ‘SYNTHESIS, CHARACTERISATION, AND INVESTIGATION OF THE ANTICANCER POTENTIAL OF CARMOFUR-LOADED SILVER NANOPARTICLES’, Journal of Istanbul Faculty of Medicine, 88(2), pp. 118-127. https://doi.org/10.26650/IUITFD.1567946 (26 Jun. 2025).


MLA

Danışman Kalındemirtaş, Ferdane, and İshak Afşin Kariper and Dilşad Özerkan and Dürdane Serap Kuruca. SYNTHESIS, CHARACTERISATION, AND INVESTIGATION OF THE ANTICANCER POTENTIAL OF CARMOFUR-LOADED SILVER NANOPARTICLES.” Journal of Istanbul Faculty of Medicine, vol. 88, no. 2, 2025, pp. 118-127. [Database Container], https://doi.org/10.26650/IUITFD.1567946


Vancouver

Danışman Kalındemirtaş F, Kariper İA, Özerkan D, Kuruca DS. SYNTHESIS, CHARACTERISATION, AND INVESTIGATION OF THE ANTICANCER POTENTIAL OF CARMOFUR-LOADED SILVER NANOPARTICLES. Journal of Istanbul Faculty of Medicine [Internet]. 26 Jun. 2025 [cited 26 Jun. 2025];88(2):118-127. Available from: https://doi.org/10.26650/IUITFD.1567946 doi: 10.26650/IUITFD.1567946


ISNAD

Danışman Kalındemirtaş, Ferdane - Kariper, İshakAfşin - Özerkan, Dilşad - Kuruca, DürdaneSerap. SYNTHESIS, CHARACTERISATION, AND INVESTIGATION OF THE ANTICANCER POTENTIAL OF CARMOFUR-LOADED SILVER NANOPARTICLES”. Journal of Istanbul Faculty of Medicine 88/2 (Jun. 2025): 118-127. https://doi.org/10.26650/IUITFD.1567946



TIMELINE


Submitted15.10.2024
Accepted10.03.2025
Published Online18.04.2025

LICENCE


Attribution-NonCommercial (CC BY-NC)

This license lets others remix, tweak, and build upon your work non-commercially, and although their new works must also acknowledge you and be non-commercial, they don’t have to license their derivative works on the same terms.


SHARE



Istanbul University Press aims to contribute to the dissemination of ever growing scientific knowledge through publication of high quality scientific journals and books in accordance with the international publishing standards and ethics. Istanbul University Press follows an open access, non-commercial, scholarly publishing.