Sisplatin ve Karboplatin Yüklü Albumin Nanopartiküllerin Meme Kanseri Hücreleri Üzerindeki Sitotoksik Etkileri

Yıl 2023, , 115 - 121, 05.03.2023

Ferdane Danışman Kalındemirtaş , İshak Afşin Kariper

https://doi.org/10.26453/otjhs.1217364

Öz

Amaç: Bu çalışmanın amacı kanser tedavisinde sıklıkla kullanılan karboplatin ve sisplatin ilaçlarının albümin nanotaşıyıcıya yüklenerek antikanser etkilerinin araştırılması ve karşılaştırılmasıdır.
Materyal ve Metot: Karboplatin (CP) ve Sisplatin (Cis) yüklenmiş albümin nanopartiküller, sırasıyla CP-NPs ve Cis-NPs olarak ultrasonikasyon kullanarak sentezlendi. Nanopartikül boyutu ve dağılımın homojenitesi Dinamik ışık saçılımı (DLS) ile değerlendirildi. Nanopartiküllerin sitotoksik aktiviteleri MDA-MB-231 ve MCF-7 meme kanseri hücrelerinde ve HUVEC hücrelerinde, MTT testi kullanılarak değerlendirildi ve morfolojik görüntüleri karşılaştırıldı.
Bulgular: CP-NPs’lerin boyutu ortalama 2-3 nm civarında iken, Cis-NPs’lerin 7-8 nm idi. Her iki nanopartikül grubunun da homojen bir şekilde dağıldığı görüldü. Sitotoksisite sonuçlarına göre CP-NPs ve Cis-NPs, MCF-7 meme kanseri hücrelerinde daha sitotoksikti. Ayrıca CP-NPs ve Cis-NPs’ler MDA-MB-231 meme kanseri hücrelerinde önemli sitotoksisite gösterirken, normal HUVEC hücrelerinde düşük sitotoksisite tespit edildi. CP-NPs ve Cis-NPs ile tedavi edilen MCF-7, tedavi edilmeyen MCF-7 ile karşılaştırıldı ve NPs'ler için istatistiksel anlamlılık P<0,01 olarak hesaplandı.
Sonuç: Meme kanseri hücrelerinde yüksek sitotoksisite gözlenirken, sağlıklı hücrelerde belirgin sitotoksisite gözlenmemiş olup albümine bağlı CP-NPs ve Cis-NPs kanser tedavisinde umut vadedici bir tedavi seçeneği olabilir.

Anahtar Kelimeler

MCF-7, MDA-MB-231, meme kanseri, nano ilaç, sitotoksisite

Cytotoxic Effects of Cisplatin and Carboplatin Loaded Albumin Nanoparticles on Breast Cancer Cells

Öz

Objective: This study aims to investigate and compare the anticancer effects of carboplatin and cisplatin, frequently used in cancer treatment, by loading them on albumin nanocarrier.
Materials and Methods: Carboplatin (CP) and Cisplatin (Cis) loaded albumin nanoparticles were synthesized using ultrasonication as CP-NPs and Cis-NPs, respectively. Nanoparticle size and distribution were evaluated by Dynamic light scattering (DLS). Cytotoxicities of NPs were evaluated in MDA-MB-231 and MCF-7 breast cancer cells and HUVEC using MTT test and their morphological images were compared.
Results: While the average size of CP-NPs was around 2-3 nm, Cis-NPs was 7-8 nm. It was observed that both NPs groups were homogeneously dispersed. According to the cytotoxicity results, both CP-NPs and Cis-NPs were more cytotoxic on MCF-7 breast cancer cells. In addition, CP-NPs and Cis-NPs showed significant cytotoxicity on MCF-7, MDA-MB-231 breast cancer cells, while low cytotoxicity was detected in normal HUVEC cells. The NPs treated MCF-7 was compared with the untreated MCF-7 and statistical significance was calculated as P<0.01 for CP-NPs and Cis-NPs.
Conclusions: Abumin-based CP-NPs and Cis-NPs showed high cytotoxicity in breast cancer cells, they have low cytotoxicity in healthy cells, making them promising for breast cancer treatment.

Anahtar Kelimeler

Cytotoxicity, breast cancer, MCF-7, MDA-MB-231, nano drug

Kaynakça

• 1. Howell A, Anderson AS, Clarke RB, et al. Risk determination and prevention of breast cancer. Breast Cancer Research 2014;16(5):1-19. doi:10.1186/S13058-014-0446-2
• 2. Reang J, Sharma PC, Kumar Thakur V, et al. Understanding the therapeutic potential of ascorbic acid in the battle to overcome cancer. Biomolecules 2021;11(8):1130. doi:10.3390/BIOM11081130
• 3. Schirrmacher V. From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment. Int J Oncol. 2019;54(2):407-419. https://doi.org/10.3892/ijo.2018.4661
• 4. Zhao CY, Cheng R, Yang Z, Tian ZM. Nanotechnology for cancer therapy based on chemotherapy. Molecules. 2018;23(4). doi:10.3390/molecules23040826
• 5. Parvanian S, Mostafavi SM, Aghashiri M. Multifunctional nanoparticle developments in cancer diagnosis and treatment. Sens Biosensing Res. 2017;13:81-87. doi:10.1016/J.SBSR.2016.08.002
• 6. Wu J. The enhanced permeability and retention (epr) effect:The significance of the concept and methods to enhance its application. Journal of Personalized Medicine 2021;11(8):771. doi:10.3390/JPM11080771
• 7. Ma P, Mumper RJ. Paclitaxel nano-delivery systems: a comprehensive review. J Nanomed Nanotechnol. 2013;4(2):1000164. doi:10.4172/2157-7439.1000164
• 8. Karami E, Behdani M, Kazemi-Lomedasht F. Albumin nanoparticles as nanocarriers for drug delivery: Focusing on antibody and nanobody delivery and albumin-based drugs. J Drug Deliv Sci Technol. 2020;55:101471. doi:10.1016/J.JDDST.2019.101471
• 9. Elzoghby AO, Samy WM, Elgindy NA. Albumin-based nanoparticles as potential controlled release drug delivery systems. Journal of Controlled Release. 2012;157(2):168-182. doi:10.1016/J.JCONREL.2011.07.031
• 10. Lee ES, Youn YS. Albumin-based potential drugs: focus on half-life extension and nanoparticle preparation. Journal of Pharmaceutical Investigation 2016;46(4):305-315. doi:10.1007/S40005-016-0250-3
• 11. Vaz J, Ansari D, Sasor A, Andersson R. SPARC: A Potential Prognostic and Therapeutic Target in Pancreatic Cancer. Pancreas. 2015;44(7):1024. doi:10.1097/MPA.0000000000000409
• 12. Kratz F. A clinical update of using albumin as a drug vehicle-A commentary. Journal of Controlled Release. 2014;190:331-336. doi:10.1016/J.JCONREL.2014.03.013
• 13. Hassanin I, Elzoghby A. Albumin-based nanoparticles: a promising strategy to overcome cancer drug resistance. Cancer Drug Resistance. 2020;3(4):930-946. doi:10.20517/CDR.2020.68
• 14. Kalındemirtaş FD, Kariper İA, Sert E, Okşak N, Kuruca SE. The evaluation of anticancer activity by synthesizing 5FU loaded albumin nanoparticles by exposure to UV light. Toxicology in Vitro 2022;84:105435. doi.org/10.1016/j.tiv.2022.105435
• 15. Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1-2):55-63. doi:10.1016/0022-1759(83)90303-4
• 16. Dang Y, Guan J. Nanoparticle-based drug delivery systems for cancer therapy. Smart Mater Med. 2020;1:10-19. doi:10.1016/J.SMAIM.2020.04.001
• 17. Liu Y, Guo Q, Sun H, Guo N, Zhang J. Improved therapeutic efficiency of photothermal treatment and nursing care in prostate cancer by DOX loaded PEG coated Cu@Se nano-hybrid vesicle. Process Biochemistry. 2020;92:78-84. doi:10.1016/J.PROCBIO.2020.02.022
• 18. Ye BL, Zheng R, Ruan XJ, Zheng ZH, Cai HJ. Chitosan-coated doxorubicin nano-particles drug delivery system inhibits cell growth of liver cancer via p53/PRC1 pathway. Biochem Biophys Res Commun. 2018;495(1):414-420. doi:10.1016/J.BBRC.2017.10.156
• 19. Haggag YA, Osman MA, El-Gizawy SA, et al. Polymeric nano-encapsulation of 5-fluorouracil enhances anti-cancer activity and ameliorates side effects in solid Ehrlich Carcinoma-bearing mice. Biomedicine & Pharmacotherapy. 2018;105:215-224. doi:10.1016/J.BIOPHA.2018.05.124
• 20. Vijayakumar S, Ganesan S. Size-dependent in vitro cytotoxicity assay of gold nanoparticles. Toxicological & Environmental Chemistry 2013;95(2):277-287. doi:10.1080/02772248.2013.770858
• 21. Kocak C, Kocak FE, Ozturk B, Tekin G, Vatansev H. Cytotoxic, anti-proliferative and apoptotic effects of noscapine on human estrogen receptor positive (MCF-7) and negative (MDA-MB-231) breast cancer cell lines. Bratisl Lek Listy. 2020;121(1):43-50. doi:10.4149/BLL_2020_007
• 22. Noh JI, Mun SK, Lim EH, et al. Induction of apoptosis in MDA-MB-231 cells treated with the methanol extract of lichen physconia hokkaidensis. Journal of Fungi 2021;7(3):188. doi:10.3390/JOF7030188
• 23. Yetisgin AA, Cetinel S, Zuvin M, Kosar A, Kutlu O. Therapeutic nanoparticles and their targeted delivery applications. Molecules. 2020;25(9). doi:10.3390/MOLECULES25092193
• 24. Zinger A, Koren L, Adir O, et al. Collagenase nanoparticles enhance the penetration of drugs into pancreatic tumors. ACS Nano. 2019;13(10):11008-11021 doi: 10.1021/acsnano.9b02395
• 25. Yan L, Shen J, Wang J, Yang X, Dong S, Lu S. Nanoparticle-based drug delivery system: a patient-friendly chemotherapy for oncology. Dose-Response. 2020;18(3). doi:10.1177/1559325820936161
• 26. Edis Z, Wang J, Waqas MK, Ijaz M, Ijaz M. Nanocarriers-mediated drug delivery systems for anticancer agents: an overview and Perspectives. Int J Nanomedicine. 2021;16:1313-1330. doi:10.2147/IJN.S289443