ORIGINAL ARTICLE Characterization of Folic Acid Surface-Coated Selenium Nanoparticles and Corresponding In Vitro and In Vivo Effects Against Breast Cancer Ahmad Reza Shahverdi, a,b,c Faranak Shahverdi, a Elnaz Faghfuri, c Mohammad Reza khoshayand, d Faranak Mavandadnejad, c Mohammad Hossein Yazdi, a and Mohsen Amini e a Biotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran b Recombinant Vaccine Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran c Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran d Department of Food and Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran e Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Received for publication January 3, 2017; accepted April 6, 2018 (ARCMED-D-16-00004). Backgrounds and Aims. Selenium nanoparticles (SeNPs) have been reported to exhibit an inhibitory effect on cancer cells. In the present study, we aimed to compare the in vitro and in vivo effects of SeNPs and folic acid surfaceecoated selenium nanoparticles (FA@- SeNPs) on breast cancer. Methods. FA@SeNPs and SeNPs were chemically synthesized and characterized with different instrumental techniques. The cytotoxicity of both nanomaterials was evaluated against 4T1 cells. In addition, the intravenous administration effect of these nanomateri- als (300 mg/week) on the lifespan and tumor size of cancer-bearing mice was investigated. Results. Although the SeNPs showed an antiproliferative effect against the cell line, the cytotoxicity of the FA@SeNPs was higher than that of the SeNPs. A low concentration of FA@SeNPs (25 mg/mL corresponding to 8.75 mg/mL of elemental SeNPs) caused approximately 68% cell mortality. In the in vivo study, the nanomaterials decreased the tumor growth rate in cancerous mice in relation to the control group. FA@SeNPs were more effective than SeNPs. Conclusions. The combination of SeNPs and FA has a potent antiproliferative effect against 4T1 cells, significantly increases the lifespan, and prevents tumor growth. Ó 2018 IMSS. Published by Elsevier Inc. Key Words: Selenium nanoparticles, Breast tumor, Tumor growth, Lifespan, Preventive strategy, Folic acid@selenium nanoparticles. Introduction Despite many advances in cancer treatment, breast cancer persists as the second leading cause of cancer-related death among women (1). Several generics in addition to preventive or therapeutic modalities have been developed to control this cancer type due to its high global inci- dence and mortality rate (1). Selenium (Se) is an essential trace element with fundamental importance for human biology and has many important biological effects partic- ularly on immune response and cancer prevention. These effects are related to Se-dependent enzyme (2) or seleno- protein functions (3). Studies demonstrated Se supple- mentation reduces the incidence of prostate, lung, and colon cancers (4,5). Selenium nanoparticles (SeNPs) are a metalloid form of Se species with newly demonstrated biological activ- ities and lower toxicity. We recently reported that the pre- ventive oral supplementation of SeNPs can lead to an increase in the immune response of Balb/c mice against breast cancer tumor cells and enhance the lifespan of tumor-bearing animals. The direct cytotoxicity of SeNPs and its conjugates have been reported against different Address reprint requests to: Ahmad Reza Shahverdi, PhD, Department of Pharmaceutical Biotechnology and Biotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Phone/Fax: (þ98) (21) 66482706; E-mail: shahverd@sina.tums.ac.ir 0188-4409/$ - see front matter. Copyright Ó 2018 IMSS. Published by Elsevier Inc. https://doi.org/10.1016/j.arcmed.2018.04.007 Archives of Medical Research - (2018) -