Sutriyo SUTRIYO, Muhammad SULAIMAN, Abdul MUN’IM

Preparation and cytotoxic activity of resveratrol-gold nanoparticles conjugated to folic acid against MCF-7 cell line

The potential benefits of resveratrol (Trans-3, 5, 4’-trihidroxy stilbene) as an anti-cancer are lowered becauseof it’s low aquous solubility, instability and low bioavailability. Recent progresses in nanoparticle technology offer apromising loophole to solve many problems in developing theurapetic agents. The ability of a nanocarrier to selectivelybring drug substances to the site of a tumor solely based on passive targeting can be enhanced by coupling a ligand tothe surface of the nanocarrier knowingly as active targeting. This research aimed to test the cytotoxic activity ofresveratrol conjugated to gold nanoparticles-folate as a carrier. Gold nanoparticles (AuNp) was chosen as a suitablecarriers to increase the potency of resveratrol (Rsv) as an anti cancer agent with the help of folic acid (FA). The expressionof folate receptors are hightened due to the excessive need of folic acid by certain types of cancer cells. Thus folic acidcan act as a targeting agent to help introduce gold nanoparticles to the target cells. Furthermore, the cytotoxic activityof the final conjugate (FA-AuNp-Rsv) will be tested against human breast cancer MCF-7 cell line using MTTcholorimetric test. Gold nanoparticles were fabricated using optimized amount of polyvinyl alcohol (PVA) as a stabilizers.FA were attached to the surface of gold nanoparticles using 4-Aminothiophenol (4-Atp) as a linker. The carboxilic groupof FA was first activated using common EDC-NHS reaction and reacted with amine group of 4-Atp to form amide bond.The physical and chemical characterization has been conducted and it was found that the final 86.9 nm nanoconjugate(FA-AuNp-Rsv) were successfuly synthesized with good stability and possesed an elevated activity (IC50=21.28 ± 1.04μM) compared to resveratrol alone (49.94 ± 1.06 μM). Thus this results were hoped to be an adequate addition to thedevelopment of nanotechnology in cancer therapy.

PDF

___

[1] Desantis CE, Jiemin, Sauer AG, Newman LA, Jemal A. Breast cancer statistics , 2017: racial disparity in mortality by state. CA Cancer J Clin. 2017; 67(6): 439–448. [CrossRef]
[2] Davidov-Pardo G, McClements DJ. Resveratrol encapsulation: designing delivery systems to overcome solubilitystability and bioavailability issues. Trends Food Sci Tech. 2014; 38(2): 88-103. [CrossRef]
[3] Murtaza G, Latif U, Najam-Ul-Haq M, Sajjad A, Karim S, Akhtar M, Hussain I. Resveratrol: an active natural compound in red wines for health. J Food Drug Anal. 2013; 21(1): 1-12. [CrossRef]
[4] Walle T, Hsieh F, DeLegge MH, Oatis jr JE, Walle UK. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos. 2004; 32(12): 1377-1382. [CrossRef]
[5] Joseph MM, Sreelekha TT. Gold nanoparticles-synthesis and application in cancer management. Recent Pat Mater Sci. 2014; 7: 8-25. [CrossRef]
[6] Brust M, Walker M, Bethell D, Schiffrin DJ, Whyman R. Synthesis of thiol-derivatised gold nanoparticles in two phase liquid-liquid system. J Chem Soc Chem Comm. 1994; 7: 801-802. [CrossRef]
[7] Alanazi FK, Radwan AA, Alsarra IA. Biopharmaceutical applications of nanogold. Saudi Pharm J. 2010; 18: 179-193. [CrossRef]
[8] Dreher MR, Liu W, Michelich CR, Dewhirst MW, Yuan F, Chilkoti A. Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers. J Natl Cancer I. 2006; 98(5): 335-344. [CrossRef]
[9] Bertrand N, Wu J, Xu X, Kamaly N, Farokhzad OC. Cancer nanotechnology: The impact of passive and active targeting in the era of modern cancer biology. Adv Drug Deliver Rev. 2014; 66: 2-25 [CrossRef]
[10] Kumar SSD, Mahesh A, Antonira MG, Rathore HS, Houreld NN, Kandasamy R. Cellular imaging and folate receptor targeting delivery of gum kondagogu capped gold nanoparticles in cancer cells. Int J Biol Macromol. 2017; 109: 220- 230. [CrossRef]
[11] Khanna PK, Gokhale R, Subbarao VVVS, Vishwanath AK, Das BK, Satyanarayana CVV. PVA stabilized gold nanoparticles by use of unexplored albeit conventional reducing agent. Mater Chem Phys. 2005; 92: 229-233. [CrossRef]
[12] Eun Jung Kim, Jeong Hyun Yeum, Jin Hyun Choi. Effects of polymeric stabilizers on the synthesis of gold nanoparticles. J Mater Sci Technol. 2014; 30(2): 107-111 [CrossRef]
[13] Joshi P, Chakraborti S, Ramirez-Vick JE, Ansari ZA, Shanker V, Chakrabarti P, Singh SP. The anticancer activity of chloroquine-gold nanoparticles against MCF-7 breast cancer cells. Colloids Surf. B. 2012; 95: 195-200. [CrossRef]
[14] Zhang Z, Jia J, Lai Y, Ma Y, Weng J, Sun L. Conjugating folic acid to gold nanoparticles through glutathione for targeting and detecting cancer cells. Bioorg Med Chem. 2010; 18: 5528–5534. [CrossRef]
[15] Mansoori GA, Brandenburg KS, Shakeri-Zadeh A. A comparative study of two folate-conjugated gold nanoparticles for cancer nanotechnology applications. Cancers. 2010; 2(4): 1911-1928. [CrossRef]
[16] Tomoaia G, Horovitz O, Mocanu A, Nita A, Avram A, Racz CP, Soritau O, Cenariu M, Tomoaia-Cotisel M. Effects of doxorubicin mediated by gold nanoparticles and resveratrol in two human cervical tumor cell lines. Colloids Surf B. 2015; 135: 726–734. [CrossRef]
[17] Kumar CG, Poornachandra Y, Mamidyala SK. Green synthesis of bacterial gold nanoparticles conjugated to resveratrol as delivery vehicles. Colloids Surf B. 2014; 123: 311-317. [CrossRef]
[18] Loutfy SA, Al-Anshary N, Abdel-Ghani NT, Hamed AR, Mohamed MB, Craik JD, Eldin TA, Abdelah AM, Hussein Y, Hasanin MTM, Elbehairi SE. Anti-proliferative activities of metalic nanoparticles in an in vitro breast cancer model. Asian Pac J Cancer Prev. 2015; 16(14): 6039-6045. [CrossRef]
[19] Selim ME, Hendi AA. Gold nanoparticles induce apoptosis in MCF-7 human breast cancer cells. Asian Pac J Cancer Prev. 2012; 13(4): 1617-1620. [CrossRef]
[20] Kim YA, Choi BT, Lee YT, Park DI, Rhee SH, Park KY, Choi YH. Resveratrol inhibits cell proliferation and induces apoptosis of human breast carcinoma MCF-7 cells. Oncol Rep. 2004; 11: 441-446. [CrossRef]
[21] Patel UB, Metha VN, Kumar MA, Kailasa SK. 4-Aminothiophenol functionalized gold nanoparticles as colorimetric sensors for the detection of cobalt using UV–Visible spectrometry. Res Chem Intermed. 2013; 39(2): 771-779. [CrossRef]
[22] Singh G, Pai RS. A rapid reversed-phase HPLC method for analysis of trans-resveratrol in PLGA nanoparticulate formulation. ISRN Chromatogr. 2014; Article ID 248635. [CrossRef]