CELLULAR UPTAKE STUDY AND CYTOTOXICITY STUDY OF RESVERATROL-GOLD-PEG-FOLATE (RSV-AU-PEG-FA) NANOPARTICLES ON HELA HUMAN CERVICAL CANCER CELL LINE

DARA A. PUTRI; SUTRIYO SUTRIYO; FADLINA C. SAPUTRI

doi:10.22159/ijap.2020v12i4.37307

Authors

DARA A. PUTRI Faculty of Pharmacy, Universitas Indonesia, Depok, 16424, West Java, Indonesia
SUTRIYO SUTRIYO Faculty of Pharmacy, Universitas Indonesia, Depok, 16424, West Java, Indonesia
FADLINA C. SAPUTRI Faculty of Pharmacy, Universitas Indonesia, Depok, 16424, West Java, Indonesia

DOI:

https://doi.org/10.22159/ijap.2020v12i4.37307

Keywords:

Resveratrol, Gold nanoparticles, Folic acid, Active targeting, Cellular uptake, Cytotoxicity, HeLa cells

Abstract

Objective: This study aimed to evaluate the effectivity of resveratrol-gold-PEG-folate (RSV-Au-PEG-FA) nanoparticles formulation in resveratrol (RSV) targeted delivery and cytotoxicity effect on HeLa human cervical cancer cell line.

Methods: Gold nanoparticles (AuNP) were used as carriers and folic acid (FA) was used as active targeting moiety, using polyethylene glycol-bis-amine (PEG-bis-amine) as linker. RSV-Au-PEG-FA nanoparticles were characterized by UV-Vis spectrophotometry, infrared spectroscopy, particle size analyzer (PSA), and transmission electron microscopy (TEM). Cellular uptake study was conducted by using fluorescence microscope. Cytotoxicity study was conducted by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.

Results: Cellular uptake study has shown that RSV-Au-PEG-FA nanoparticles are potential to be accumulated intracellularly in HeLa cells more than in Vero cells. Cytotoxicity study has shown RSV-Au-PEG-FA nanoparticles IC₅₀ 67.06±2.14 mM and RSV IC₅₀ 9.66±1.44 mM on HeLa cells

Conclusion: RSV-Au-PEG-FA nanoparticles are potential to enhance RSV uptake by HeLa cells selectively.

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References

Tani H, Hikami S, Iizuna S, Yoshimatsu M, Asama T, Ota H, et al. Pharmacokinetics and safety of resveratrol derivatives in humans after oral administration of melinjo (Gnetum gnemon L.) seed extract powder. J Agric Food Chem 2014;62:1999-2007.

Tatefuji T, Yanagihara M, Fukushima S, Hashimoto K. Safety assessment of melinjo (Gnetum gnemon L.) seed extract: acute and subchronic toxicity studies. Food Chem Toxicol 2014;67:230-5.

Robinson K, Mock C, Liang D. Pre-formulation studies of resveratrol. Drug Dev Ind Pharm 2015;41:1464-9.

Dhandayuthapani S, Marimuthu P, Hormann V, Kumi Diaka J, Rathinavelu A. Induction of apoptosis in HeLa cells via caspase activation by resveratrol and genistein. J Med Food 2013;16:139-46.

Li L, Qiu RL, Lin Y, Cai Y, Bian Y, Fan Y, et al. Resveratrol suppresses human cervical carcinoma cell proliferation and elevates apoptosis via mitochondrial and p53 signalling pathways. Oncol Lett 2018;15:9845-51.

Flores Perez A, Elizondo G. Apoptosis induction and inhibition of HeLa cell proliferation by alpha-naphthoflavone and resveratrol are aryl hydrocarbon receptor-independent. Chem Biol Interact 2018;281:98-105.

Kim YS, Sill JW, Sung HJ. Suppressing effect of resveratrol on the migration and invasion of human metastatic lung and cervical cancer cells. Mol Biol Rep 2012;39:8709-16.

Mukherjee S, Dudley JI, Das DK. Dose-dependency of resveratrol in providing health benefits. Dose Response 2010;8:478-500.

Fujimoto A, Sakanashi Y, Matsui H, Oyama T, Nishimura Y, Masuda T, et al. Cytometric analysis of cytotoxicity of polyphenols and related phenolics to rat thymocytes: potent cytotoxicity of resveratrol to normal cells. Basic Clin Pharmacol Toxicol 2009;104:455-62.

Ferry Dumazet H, Garnier O, Mamani Matsuda M, Vercauteren J, Belloc F, Billiard C, et al. Resveratrol inhibits the growth and induces the apoptosis of both normal and leukemic hematopoietic cells. Carcinogenesis 2002;3:1327-33.

Billack B, Radkar V, Adiabouah C. In vitro evaluation of the cytotoxic and anti-proliferative properties of resveratrol and several of its analogs. Cell Mol Biol Lett 2008;12:553-69.

Battacharya R, Patra CR, Earl A, Wang S, Katarya A, Lu L, et al. Attaching folic acid on gold nanoparticles using noncovalent interaction via different polyethylene glycol backbones and targeting of cancer cells. Nanomed: NBM 2007;3:224-38.

Das M, Shim KH, An SSA, Yi DK. Review on gold nanoparticles and their applications. Toxicol Environ Health Sci 2011;3:193-205.

Kumar CG, Poornachandra Y, Mamidyala SK. Green synthesis of bacterial gold nanoparticles conjugated to resveratrol as delivery vehicles. Colloids Surf B 2014;123:311-7.

Sutriyo, Mutalib A, Ristaniah, Anwar E, Radji M, Pujiyanto A, et al. Synthesis of gold nanoparticles with polyamidoamine (PAMAM) generation 4 dendrimer as stabilizing agent for CT scan contrast agent. Macromol Symp 2015;353:96-101.

Sonvico F, Dubernet C, Marsaud V, Appel M, Chacun H, Stella B, et al. Establishment of an in vitro model expressing the folate receptor for the investigation of targeted delivery systems. J Drug Delivery Sci Technol 2005;15:407-10.

Liu F, Deng D, Chen X, Qian Z, Achilefu S, Gu Y. Folate-polyethylene glycol conjugated near-infrared fluorescence probe with high targeting affinity and sensitivity for in vitro early tumor diagnosis. Mol Imaging Biol 2010;12:595-607.

Zwicke GL, Mansoori GA, Jeffery CJ. Utilizing the folate receptor for active targeting of cancer nanotherapeutics. Nano Rev 2012;18496:1-11.

Banu H, Stanley B, Faheem SM, Seenivasan R, Premkumar K, Vasanthakumar G. Thermal chemosensitization of breast cancer cells to cyclophosphamide treatment using folate receptor targeted nanoparticles. Plasmonics 2014;9:1341-9.

Sutriyo S, Iswandana R, Ivariani FM. Synthesis and stability of resveratrol-gold nanoparticle-polyethylene glycol-folic acid conjugates. Int J Appl Pharm 2020;12:237-41.

Sadhasivam S, Savitha S, Wu CJ, Lin FH, Stobinski L. Carbon encapsulated iron oxide nanoparticles surface engineered with polyethylene glycol-folic acid to induce selective hyperthermia in folate over expressed cancer cells. Int J Pharm 2015;480:8-14.

Rahme K, Chen L, Hobbs RG, Morris MA, O’Driscoll C, Holmes JD. PEGylated gold nanoparticles: polymer quantification as a function of PEG lengths and nanoparticle dimensions. RSV Adv 2013;3:6085-94.

Souto AA, Carneiro MC, Seferin M, Senna MJH, Conz A, Gobbi K. Determination of trans-resveratrol concentrations in brazilian red wines by HPLC. J Food Compost Anal 2001;14:441-5.

Marcsek ZL, Kocsis Z, Szende B, Tompa. Effect of formaldehyde and resveratrol on the viability of Vero, HepG2, and MCF-7 cells. Cell Bio Int 2007;31:1214-9.

Washington KE, Kularatne RN, Biewer MC, Stefan MC. Combination loading of doxorubicin and resveratrol in polymeric micelles for increased loading efficiency and efficacy. ACS Biomater Sci Eng 2018;4:997-1004.

Yang G, Xiang S, Zhang K, Gao D, Zeng C, Zhao F. Breast cancer imaging with fluorescein isothiocyanate-modified gold nanoparticles in vitro and in vivo. Int J Clin Exp Med 2016;9:753-9.

Larasati YA, Putri DDP, Utomo RY, Hermawan A, Meiyanto E. Combination of cisplatin and cinnamon essential oil inhibits HeLa cells proliferation through cell cycle arrest. J Appl Pharm Sci 2014;4:14-9.

Chatterjee K, Al-Sharif D, Mazza C, Syar P, Al-Sharif M, Fata JE. Resveratrol and pterostilbene exhibit anticancer properties involving downregulation of HPV oncoprotein E6 in cervical cancer cells. Nutrients 2018;10:243.

Capek I. Chapter 2: noble metal nanoparticles. Nan Sci Tech; 2017. p. 125-210.

Liu F, Deng D, Chen X, Qian Z, Achilefu S, Gu Y. Folate-polyethylene glycol conjugated near-infrared fluorescence probe with high targeting affinity and sensitivity for in vitro early tumor diagnosis. Mol Imaging Biol 2010;12:595-607.

Hao J, Tong T, Jin K, Zhuang Q, Han T, Bi Y, et al. Folic acid-functionalized drug delivery platform of resveratrol based on Pluronic 127/D--tocopheryl polyethyle glycol 1000 succinate mixed micelles. Int J Nanomed 2017;12:2279-92.

Kakkar D, Tiwari AK, Chuttani K, Kumar R, Mishra K, Singh H, et al. Polyethylene-glycolylated isoniazid conjugate for reduced toxicity and sustained release. Ther Delivery 2011;2:205-12.

Jain S, Rathi VV, Das M, Godugu C. Folate-decorated PLGA nanoparticles as a rationally designed vehicle for the oral delivery of insulin. Nanomedicine 2012;7:1311-37.

Danaei M, Dehghankhold M, Ataei S, Davarani FH, Javanmard R, Dokhani A, et al. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics 2018;10:57.

Sun D, Kang S, Liu C, Lu Q, Cui L, Hu B. Effect of zeta potential and particle size on the stability of SiO2 nanospheres as carrier for ultrasound imaging contrast agents. Int J Electrochem Sci 2016;11:8520-9.

Fröhlich E. The role of surface charge in cellular uptake and cytotoxicity on medical nanoparticles. Int J Nanomed 2012;7:5577-91.

Toy R, Peiris PM, Ghaghada KB, Karathanasis E. Shaping cancer nanomedicine: the effect of particle shape on the in vivo journey of nanoparticles. Nanomed (Lond) 2014;9:121-34.

Chithrani BD, Ghazani AA, Chan WCW. Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett 2006;6:662-8.

Leamon CP, Low PS. Folate-mediated targeting: from diagnostic to drug and gene delivery. Drug Discovery Today 2001;6:44-51.

Sulaiman M, Sutriyo S, Mun’im A. Preparation and cytotoxic activity of resveratrol-gold nanoparticles conjugated to folic acid against MCF-7 cell line. J Res Pharm 2019;23:927-34.

Wamsley A. Chapter 12: ligand-based targeting approaches to drug delivery. Design of Controlled Release Drug Delivery Systems. California: McGraw-Hill; 2006.

Rosenblum D, Joshi N, Tao W, Karp JM, Peer D. Progress and challenges towards targeted delivery of cancer therapeutics. Nat Commun 2018;9:1410.

Kumar P, Roy I. Applications of gold nanoparticles in clinical medicine. Int J Pharm Pharm Sci 2016;8:9-16.