بررسی اثرسلول کشی نانوذرات بیولوژیک طلا حامل لیگاند فولات و داروی کربوپلاتین بر سرطان تخمدان
محورهای موضوعی : فصلنامه زیست شناسی جانوری
مهناز نوری
1
,
غزل عشقی
2
,
بهروز یحیایی
3
,
پارمیدا سراج
4
,
زهرا نادیا شریفی
5
*
1 - گروه زنان و زایمان، دانشکده پزشکی، دانشگاه آزاد اسلامی، واحد شاهرود، شاهرود، ایران
2 - گروه علوم تشریح و علوم اعصاب شناختی، دانشکده پزشکی، دانشگاه علوم پزشکی آزاد اسلامی، تهران، ایران
3 - گروه پزشکی، واحد شاهرود، دانشگاه آزاد اسلامی، شاهرود، ایران
4 - گروه علوم تشریح و علوم اعصاب شناختی دانشگاه علوم پزشکی آزاد اسلامی تهران- ایران
5 - دپارتمان علوم تشریحی- دانشگاه علوم پزشکی آزاد اسلامی تهران
کلید واژه: نانوذرات بیولوژیک طلا, لیگاند فولات, کربوپلاتین, سلول های رده A2780,
چکیده مقاله :
نانوفناوری به‌عنوان دانشی نوین و چندرشته‌ای، تحول قابل‌توجهی در حوزه پزشکی، به‌ویژه در درمان‌های هدفمند سرطان ایجاد کرده است. یکی از مهم‌ترین دستاوردهای این فناوری، طراحی نانوذراتی با قابلیت شناسایی و هدف‌گیری اختصاصی سلول‌های سرطانی می‌باشد. هدف از این مطالعه، بررسی اثرات سیتوتوکسیک نانوذرات بیولوژیک طلای حاوی لیگاند فولات و داروی کربوپلاتین بر سلول‌های سرطانی رده A2780 است. ابتدا نانوذرات طلا سنتز و با لیگاند فولات اصلاح شدند. سپس میزان ورود این نانوذرات به سلول و سمیت آن‌ها با استفاده از آزمون‌های MTT و طیف‌سنجی ICP ارزیابی گردید. نتایج نشان داد که فولات به‌طور مؤثر به نانوذرات متصل شده است، به‌طوری که شیفت اندک پیک‌های جذبی در طیف جذب فولات، حاکی از ایجاد پیوند میان فولات و نانوذره می‌باشد. همچنین، تحلیل ICP حضور نانوذرات طلا در داخل سلول‌ها را تأیید کرد که بیانگر ورود موفق این نانوسامانه‌ها به سلول‌های هدف است. این یافته‌ها نشان می‌دهد که نانوذرات طلا با لیگاند فولات می‌توانند به‌عنوان حامل‌های دارویی مؤثر برای انتقال انتخابی داروی کربوپلاتین به سلول‌های سرطانی تخمدان به کار روند و به‌کارگیری آن‌ها در درمان سرطان می‌تواند موجب افزایش اثربخشی درمان و کاهش عوارض جانبی گردد.
Nanotechnology, as a novel and multidisciplinary field, has brought significant advancements in medicine, particularly in targeted cancer therapies. One of its most important achievements is the development of nanoparticles capable of specifically identifying and targeting cancer cells. This study aims to investigate the cytotoxic effects of biologically synthesized gold nanoparticles conjugated with folate ligand and loaded with the chemotherapeutic agent carboplatin on A2780 ovarian cancer cell lines. Gold nanoparticles were first synthesized and subsequently functionalized with folate. The cellular uptake and cytotoxicity of these nanoparticles were evaluated using MTT assay and ICP spectroscopy. The results demonstrated successful conjugation of folate to the nanoparticles, indicated by minor shifts in the absorption peaks in the folate spectrum, suggesting stable binding. Moreover, ICP analysis confirmed the presence of gold within the cells, verifying the effective internalization of both drug-loaded and bare nanoparticles. These findings suggest that gold nanoparticles functionalized with folate ligands can serve as efficient drug delivery carriers for the selective transport of carboplatin into ovarian cancer cells. The use of such targeted nanocarriers holds promise for enhancing therapeutic efficacy while minimizing systemic side effects.
.
1. López-Soto A, Gonzalez S, Smyth MJ, Galluzzi L. Control of Metastasis by NK Cells. Cancer Cell. 2017;32(2):135-54.
2. Gallaher JA, Enriquez-Navas PM, Luddy KA, Gatenby RA, Anderson ARA. Spatial Heterogeneity and Evolutionary Dynamics Modulate Time to Recurrence in Continuous and Adaptive Cancer Therapies. Cancer Res. 2018;78(8):2127-39.
3. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12-49.
4. Mortezaee K, Salehi E, Mirtavoos-Mahyari H, Motevaseli E, Najafi M, Farhood B, et al. Mechanisms of apoptosis modulation by curcumin: Implications for cancer therapy. J Cell Physiol. 2019;234(8):12537-50.
5. Ebell MH, Culp MB, Radke TJ. A Systematic Review of Symptoms for the Diagnosis of Ovarian Cancer. American Journal of Preventive Medicine. 2016;50(3):384-94.
6. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021;71(1):7-33.
7. Board E. Female genital tumours. WHO Classification of Tumours (International Agency for Research on Cancer). 2020.
8. Narod S. Can advanced-stage ovarian cancer be cured? Nature Reviews Clinical Oncology. 2016;13(4):255-61.
9. Zhang C, Xu C, Gao X, Yao Q. Platinum-based drugs for cancer therapy and anti-tumor strategies. Theranostics. 2022;12(5):2115-32.
10. Damia G, Broggini M. Platinum resistance in ovarian cancer: role of DNA repair. Cancers. 2019;11(1):119.
11. Thigpen T, Shingleton H, Homesley H, LaGasse L, Blessing J. cis-Dichlorodiammineplatinum(II) in the treatment of gynecologic malignancies: phase II trials by the Gynecologic Oncology Group. Cancer Treat Rep. 1979;63(9-10):1549-55.
12. Prat J, Mutch DG. Pathology of cancers of the female genital tract including molecular pathology. International Journal of Gynecology & Obstetrics. 2018;143:93-108.
13. Prat J, D'Angelo E, Espinosa I. Ovarian carcinomas: at least five different diseases with distinct histological features and molecular genetics. Hum Pathol. 2018;80:11-27.
14. Ali ES, Sharker SM, Islam MT, Khan IN, Shaw S, Rahman MA, et al. Targeting cancer cells with nanotherapeutics and nanodiagnostics: Current status and future perspectives. Semin Cancer Biol. 2021;69:52-68.
15. Sun L, Liu H, Ye Y, Lei Y, Islam R, Tan S, et al. Smart nanoparticles for cancer therapy. Signal transduction and targeted therapy. 2023;8(1):418.
16. 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):2943-70.
17. Ramalingam V. Multifunctionality of gold nanoparticles: Plausible and convincing properties. Adv Colloid Interface Sci. 2019;271:101989.
18.
19. Malik S, Muhammad K, Waheed Y. Emerging Applications of Nanotechnology in Healthcare and Medicine. Molecules. 2023;28(18).
20. Alrushaid N, Khan FA, Al-Suhaimi EA, Elaissari A. Nanotechnology in Cancer Diagnosis and Treatment. Pharmaceutics. 2023;15(3).
21. Giannakou C, Park MV, de Jong WH, van Loveren H, Vandebriel RJ, Geertsma RE. A comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements. Int J Nanomedicine. 2016;11:2935-52.
22. Wilhelm S, Tavares AJ, Dai Q, Ohta S, Audet J, Dvorak HF, et al. Analysis of nanoparticle delivery to tumours. Nature reviews materials. 2016;1(5):1-12.
23. Blanco E, Shen H, Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nature biotechnology. 2015;33(9):941-51.
24. Nag OK, Delehanty JB. Active cellular and subcellular targeting of nanoparticles for drug delivery. Pharmaceutics. 2019;11(10):543.
25. Oliva N, Carcole M, Beckerman M, Seliktar S, Hayward A, Stanley J, et al. Regulation of dendrimer/dextran material performance by altered tissue microenvironment in inflammation and neoplasia. Science translational medicine. 2015;7(272):272ra11-ra11.
26. Kang MS, Lee SY, Kim KS, Han DW. State of the Art Biocompatible Gold Nanoparticles for Cancer Theragnosis. Pharmaceutics. 2020;12(8).
27. Capek I. Polymer decorated gold nanoparticles in nanomedicine conjugates. Adv Colloid Interface Sci. 2017;249:386-99.
28. Younis NK, Roumieh R, Bassil EP, Ghoubaira JA, Kobeissy F, Eid AH. Nanoparticles: Attractive tools to treat colorectal cancer. Semin Cancer Biol. 2022;86(Pt 2):1-13.
29. Younis NK, Ghoubaira JA, Bassil EP, Tantawi HN, Eid AH. Metal-based nanoparticles: Promising tools for the management of cardiovascular diseases. Nanomedicine. 2021;36:102433.
30. Boehnke N, Straehla JP, Safford HC, Kocak M, Rees MG, Ronan M, et al. Massively parallel pooled screening reveals genomic determinants of nanoparticle delivery. Science. 2022;377(6604):eabm5551.
31. Rana A, Bhatnagar S. Advancements in folate receptor targeting for anti-cancer therapy: A small molecule-drug conjugate approach. Bioorg Chem. 2021;112:104946.
32. Siddique S, Chow JC. Gold nanoparticles for drug delivery and cancer therapy. Applied Sciences. 2020;10(11):3824.
33. Sharifi M, Attar F, Saboury AA, Akhtari K, Hooshmand N, Hasan A, et al. Plasmonic gold nanoparticles: Optical manipulation, imaging, drug delivery and therapy. J Control Release. 2019;311-312:170-89.
34. Lopes TS, Alves GG, Pereira MR, Granjeiro JM, Leite PEC. Advances and potential application of gold nanoparticles in nanomedicine. J Cell Biochem. 2019;120(10):16370-8.
35. Yafout M, Ousaid A, Khayati Y, El Otmani IS. Gold nanoparticles as a drug delivery system for standard chemotherapeutics: A new lead for targeted pharmacological cancer treatments. Scientific African. 2021;11.
36. Srivastava AK. 9 - The role of fungus in bioactive compound production and nanotechnology. In: Kumar A, Singh AK, Choudhary KK, editors. Role of Plant Growth Promoting Microorganisms in Sustainable Agriculture and Nanotechnology: Woodhead Publishing; 2019. p. 145-62.
37. Rai M, Bonde S, Golinska P, Trzcińska-Wencel J, Gade A, Abd-Elsalam KA, et al. Fusarium as a Novel Fungus for the Synthesis of Nanoparticles: Mechanism and Applications. J Fungi (Basel). 2021;7(2).
38. Goddard ZR, Marín MJ, Russell DA, Searcey M. Active targeting of gold nanoparticles as cancer therapeutics. Chemical Society Reviews. 2020;49(23):8774-89.
39. Zwicke GL, Ali Mansoori G, Jeffery CJ. Utilizing the folate receptor for active targeting of cancer nanotherapeutics. Nano reviews. 2012;3(1):18496.
40. Kue CS, Kamkaew A, Burgess K, Kiew LV, Chung LY, Lee HB. Small molecules for active targeting in cancer. Medicinal research reviews. 2016;36(3):494-575.
41. Assaraf YG, Leamon CP, Reddy JA. The folate receptor as a rational therapeutic target for personalized cancer treatment. Drug Resistance Updates. 2014;17(4-6):89-95.
42. Tagde P, Kulkarni GT, Mishra DK, Kesharwani P. Recent advances in folic acid engineered nanocarriers for treatment of breast cancer. Journal of Drug Delivery Science and Technology. 2020;56:101613.
.43 Ak G, Yilmaz H, Güneş A, Hamarat Sanlier S. In vitro and in vivo evaluation of folate receptor-targeted a novel magnetic drug delivery system for ovarian cancer therapy. Artif Cells Nanomed Biotechnol. 2018;46(sup1):926-937.
44. Li S, Li X, Ding J, Han L, Guo X. Anti-tumor efficacy of folate modified PLGA-based nanoparticles for the co-delivery of drugs in ovarian cancer. Drug Des Devel Ther. 2019;13:1271-80.
45. Staff NP, Fehrenbacher JC, Caillaud M, Damaj MI, Segal RA, Rieger S. Pathogenesis of paclitaxel-induced peripheral neuropathy: A current review of in vitro and in vivo findings using rodent and human model systems. Exp Neurol. 2020;324:113121.