Preparation and Characterization of PEGylated Iron Oxide-Gold Nanoparticles for Delivery of Sulforaphane and Curcumin

Abstract

Natural products have been used for the treatment of various diseases such as cancer. Curcumin (CUR) and sulforaphane (SF) have anti-cancer effects, but their application is restricted because of their low water solubility and poor oral bioavailability. To improve the bioavailability and solubility of SF and CUR, we performed an advanced delivery of SF and CUR with PEGylated gold coated Fe₃O₄ magnetic nanoparticles (PEGylated Fe₃O₄@Au NPs) to endorse SF and CUR maintenance as an effective and promising antitumor drugs. The structure of the synthesized nanocarrieris evaluated by, transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FT-IR). The results revealed that the size of NPs was 20 nm. They were mono-dispersed in water, with high drug-loading capacity and stability. CUR and SF were encapsulated into NPs with loading capacity of 16.32±0.023% and 15.74±0.015% and entrapment efficiency of 74.57±0.14% and 72.20±0.18% respectively. The in-vitro study of SF and CUR loaded PEGylated Fe₃O₄@Au NPs on human breast adenocarcinoma cell line (SK-BR-3) confirmed that cytotoxicity of SF and CUR can enhance when they are loaded on PEGylated Fe₃O₄@Au NPs in comparison to Free SF and void CUR. The results of flow cytometry and real-time PCR shown that nano-carriers can increase therapeutic effects of SF and CUR by apoptosis and necrosis induction as well as inhibiting of migration in SK-BR-3 cell line.

Key words

sulforaphane - apoptosis - breast cancer - curcumin - PEGylated gold-coated Fe₃O₄ nanoparticles

• References

• 1 Fan L, Strasser-Weippl K, Li St J-J. et al. Breast cancer in China. The lancet oncology 2014; 15: e279-e289
• 2 Kenyon M, Mayer DK, Owens AK. Late and long-term effects of breast cancer treatment and surveillance management for the general practitioner. Journal of Obstetric, Gynecologic, & Neonatal Nursing 2014; 43: 382-398
• 3 Gaafer NM. Evaluation of Vitamin D and phosphate levels in serum of breast cancer patients in Khartoum State: Alzaeim Alazhari University. 2015;
• 4 Kelsey JL, Gammon MD, John EM. Reproductive factors and breast cancer. Epidemiologic reviews 1993; 15: 36-47
• 5 Poorhosseini S, Hashemi M, Alipour ON. et al. New gene profiling in determination of breast cancer recurrence and prognosis in iranian women. Asian Pacific journal of cancer prevention: APJCP 2016; 17: 155-160
• 6 Kerbel RS. Tumor angiogenesis: Past, present and the near future. Carcinogenesis 2000; 21: 505-515
• 7 Park EH, Joo MH, Kim SH. et al. Antiangiogenic activity of Gardenia jasminoides fruit. Phytotherapy Research. 2003; 17: 961-962
• 8 Manjili H, Malvandi H, Mousavi M-S. et al. Preparation and physicochemical characterization of biodegradable mPEG-PCL coreshell micelles for delivery of artemisinin. Pharm Sci 2016; 22: 234-243
• 9 Cartea ME, Velasco P. Glucosinolates in Brassica foods: bioavailability in food and significance for human health. Phytochemistry reviews 2008; 7: 213-229
• 10 Kheiri Manjili H, Sharafi A, Attari E. et al. Pharmacokinetics and in vitro and in vivo delivery of sulforaphane by PCL–PEG–PCL copolymeric-based micelles. Artificial Cells. Nanomedicine, and Biotechnology 2017; 1-12 doi:10.1080/21691401.2017.1282501
• 11 Donaldson MS. Nutrition and cancer: a review of the evidence for an anti-cancer diet. Nutrition journal 2004; 3: 19
• 12 Clarke JD, Dashwood RH, Ho E. Multi-targeted prevention of cancer by sulforaphane. Cancer letters 2008; 269: 291-304
• 13 Li Y, Zhang T. Targeting cancer stem cells with sulforaphane, a dietary component from broccoli and broccoli sprouts. Future oncology 2013; 9: 1097-1103
• 14 Manjili H, Malvandi H, Mousavi M-S. et al. In vitro and in vivo delivery of artemisinin loaded PCL–PEG–PCL micelles and its pharmacokinetic study. Artificial cells, nanomedicine, and biotechnology 2017;
• 15 Danafar H, Sharafi A, Kheiri Manjili H. et al. Sulforaphane delivery using mPEG–PCL co-polymer nanoparticles to breast cancer cells. Pharmaceutical development and technology 2017; 22: 642-651
• 16 Cheung KL, Khor TO, Kong A-N. Synergistic effect of combination of phenethyl isothiocyanate and sulforaphane or curcumin and sulforaphane in the inhibition of inflammation. Pharmaceutical research 2009; 26: 224-231
• 17 Vareed SK, Kakarala M, Ruffin MT. et al. Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects. Cancer Epidemiology and Prevention Biomarkers 2008; 17: 1411-1417
• 18 Jäger R, Lowery RP, Calvanese AV. et al. Comparative absorption of curcumin formulations. Nutrition journal 2014; 13: 11
• 19 Manjili HK, Ghasemi P, Malvandi H. et al. Pharmacokinetics and in vivo delivery of curcumin by copolymeric mPEG-PCL micelles. European Journal of Pharmaceutics and Biopharmaceutics. 2017; 116: 17-30
• 20 Anand P, Kunnumakkara AB, Newman RA. et al. Bioavailability of curcumin: problems and promises. Molecular pharmaceutics 2007; 4: 807-818
• 21 Danafar H, Rostamizadeh K, Hamidi M. Polylactide/poly (ethylene glycol)/polylactide triblock copolymer micelles as carrier for delivery of hydrophilic and hydrophobic drugs: A comparison study. Journal of Pharmaceutical Investigation 2017;
• 22 Manjili HK, Ma’mani L, Tavaddod S. et al. D, L-Sulforaphane loaded Fe₃O₄@ Gold Core Shell Nanoparticles: A Potential Sulforaphane Delivery System. PloS one 2016; 11: e0151344
• 23 Porbarkhordari E, Foladsaz K, Hoseini SH. et al. The hypoglycemic effects of an ethanol extract of peganum harmala in streptozotocin-induced diabetic rats. Iranian Journal of Pharmaceutical Sciences 2014; 10: 47-54
• 24 Nomani A, Nosrati H, Manjili HK. et al. Preparation and characterization of copolymeric polymersomes for protein delivery. Drug Research 2017;
• 25 Danafar H, Manjili H, Najafi M. Study of copolymer composition on drug loading efficiency of enalapril in polymersomes and cytotoxicity of drug loaded nanoparticles. Drug Research 2016; 66: 495-504
• 26 Gharebaghi F, Dalali N, Ahmadi E. et al. Preparation of wormlike polymeric nanoparticles coated with silica for delivery of methotrexate and evaluation of anticancer activity against MCF7 cells. Journal of Biomaterials Applications 2017; 31: 1305-1316
• 27 Ahmed S, Ahmad M, Swami BL. et al. A review on plants extract mediated synthesis of silver nanoparticles for antimicrobial applications: a green expertise. Journal of advanced research 2016; 7: 17-28
• 28 Danafar H, Hamidi M. 2015. Pharmacokinetics and bioequivalence study of amlodipine and atorvastatin in healthy male volunteers by LC-MS. Pharm Sci. 2015; 21: 167-174
• 29 Cheng L, Wang C, Ma X. et al. Multifunctional upconversion nanoparticles for dual-modal imaging-guided stem cell therapy under remote magnetic control. Adv Funct Mater. 2013; 23: 272-280
• 30 Danafar H. Applications of copolymeric nanoparticles in drug delivery systems. Drug Research 2016; 66: 506-519
• 31 Hoskins C, Min Y, Gueorguieva M. et al. Hybrid gold-iron oxide nanoparticles as a multifunctional platform for biomedical application. Journal of nanobiotechnology 2012; 10: 27
• 32 Khoee S, Kavand A. A new procedure for preparation of polyethylene glycol-grafted magnetic iron oxide nanoparticles. Journal of Nanostructure in Chemistry 2014; 4: 1-6
• 33 Kumagai M, Sarma TK, Cabral H. et al. Enhanced in vivo magnetic resonance imaging of tumors by pegylated iron-oxide–gold core–shell nanoparticles with prolonged blood circulation properties. Macromolecular rapid communications 2010; 31: 1521-1528
• 34 Danafar H, Rostamizadeh K, Davaran S. et al. Drug-conjugated PLA–PEG–PLA copolymers: A novel approach for controlled delivery of hydrophilic drugs by micelle formation. Pharmaceutical development and technology 2015;
• 35 Izadi A, Manjili HK, Ma’mani L. et al. Sulforaphane loaded pegylated iron oxide-gold core shell nanoparticles: A promising delivery system for cancer therapy. American International Journal of Contemporary Scientific Research 2015; 2: 84-94
• 36 Danafar H, Hamidi M. A rapid and sensitive LC–MS method for determination of ezetimibe concentration in human plasma: Application to a bioequivalence study. Chromatographia 2013; 23: 1667-1675
• 37 Choi S, Lew KL, Xiao H. et al. D, L-Sulforaphane-induced cell death in human prostate cancer cells is regulated by inhibitor of apoptosis family proteins and Apaf-1. Carcinogenesis 2007; 28: 151-162
• 38 Park SY, Kim GY, Bae S-J. et al. Induction of apoptosis by isothiocyanate sulforaphane in human cervical carcinoma HeLa and hepatocarcinoma HepG2 cells through activation of caspase-3. Oncol Rep. 2007; 18: 181-187