Selenium as a pleiotropic agent for medical discovery and drug delivery

International Journal of Nanomedicine Dovepress open access to scientific and medical research Review International Journal of Nanomedicine downloaded from https://www.dovepress.com/ by 37.59.46.207 on 21-Dec-2018 For personal use only. Open Access Full Text Article Selenium as a pleiotropic agent for medical discovery and drug delivery This article was published in the following Dove Press journal: International Journal of Nanomedicine Baozhang Guan 1,* Ruiling Yan 2,* Ruiman Li 3 Xingwang Zhang 4 Department of Nephrology, The First Affiliated Hospital of Jinan University, Guangzhou, China; 2Fetal Medicine Department, The First Affiliated Hospital of Jinan University, Guangzhou, China; 3Department of Gynecology and Obstetrics, The First Affiliated Hospital of Jinan University, Guangzhou, China; 4Department of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou, China 1 *These authors contributed equally to this work Correspondence: Xingwang Zhang Department of Pharmaceutics, College of Pharmacy, Jinan University, 601 West Huangpu Avenue, Guangzhou 510632, China Email Ruiman Li Department of Gynecology and Obstetrics, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China Email Introduction Selenium is a trace element that is essential for human health. In recent years, the health benefits of selenium have been gradually recognized.1 Deficiency of nutrient selenium frequently results in the incidence of various disorders, such as diabetes, Keshan disease, thyroid dysfunction, arthrophyma, and cognitive limitation.2 Natural selenium is present in the soil and assimilated into various plants, including seeds, nuts, vegetables, and mushrooms. The human body receives selenium through the dietary intake of selenium-rich foodstuffs. The selenium content in the soil is geographically distributed unevenly on the global horizon. Selenium deficiency approximately affects 500 million to 1 billion people worldwide. Selenium exists in the human body in the form of selenoproteins, which can be derived from ingested organic or inorganic selenium. Organic selenium (mainly selenomethionine) and ionic selenium (eg, selenite and selenate) are highly bioavailable, but elemental selenium is difficult to absorb by the gastrointestinal tract unless nanosized.3 Organic selenium from foods is relatively safe for the human body, whereas the inorganic one supplemented with chemicals exhibits a narrow window from therapeutic effect to toxic effect.4 Once being absorbed into the circulatory system, selenium will bind with various proteins in vivo to form Se/protein complexes, ie, selenoproteins, to exert the physiological actions. However, residents in the area that lacks selenium have the difficulty to assimilate enough naturally occurring selenium from the daily diet. Hence, some diseases associated with selenium deficiency occur.5–9 For these people, selenium supplementation becomes a crucial measure, which needs to be performed. Currently, selenium is not only utilized as a nutritional supplement for 7473 submit your manuscript | www.dovepress.com International Journal of Nanomedicine 2018:13 7473–7490 Dovepress © 2018 Guan et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://dx.doi.org/10.2147/IJN.S181343 Powered by TCPDF (www.tcpdf.org) Abstract: Selenium as a biologically active element lends much support to health maintenance and disease prevention. It is now presenting pleiotropic effects on therapy and drug delivery. In this study, a profiling on the physiological functions, therapeutic significances, clinical/preclinical performances, and biomedical and drug delivery applications of selenium in different modalities was carried out. Major interests focused on selenium-based nanomedicines in confronting various diseases pertaining to selenium or not, especially in antitumor and antidiabetes. Furthermore, the article exclusively discusses selenium nanoparticles featured by ameliorative functions with emphasis on their applications in medical practice and drug delivery. The state-of-the-art in medical discovery as well as research and development on selenium and nano-selenium is discussed in this review. Keywords: selenium, selenium nanoparticles, nanomedicine, biomedical applications, drug delivery, oncotherapy, diabetes Dovepress disease prevention and treatment but also applied for drug delivery in the form of nanoparticles to potentiate the carried therapeuticals. It is often delighted to anticipate a synergistic effect occurring between selenium and the payload.10,11 Selenium as a pleiotropic agent has attracted considerable attention for biotherapy and drug delivery. In particular, significant progresses in nanotechnology greatly escalate the translation of Se-based nanomedicines. In this study, we carried out a systematic literature review concerning selenium and discussed its physiological functions, therapeutic potential against relevant diseases, Se-based nanomedicines for cancer, and diabetes mellitus (DM) as well as selenium nanoparticles (SeNPs) for various medical purposes. Special interests focused on the pharmaceutical applications of SeNPs as drug delivery carriers with the highlight of encouraging outcomes. relevant to oxidative stress,12 such as DM, atherosclerosis, and fatty liver. The effect of selenium on oxidative stress is realized by selenoproteins.13 Selenoproteins are proteins that include a selenocysteine (Sec) residue. Approximately 25 kinds of different selenoproteins have been observed in human cells and tissues so far. Among functionally characterized selenoproteins, there are five glutathione peroxidases (GPx) and three thioredoxin reductases (TrxR) with one Sec residue in structure. Selenoprotein P (SEPP) that contains 10 Sec residues is the most common selenoprotein found in the plasma. The lack of selenium deprives the ability of the cells to synthesize selenoproteins; therefore, many health effects of low selenium intake are believed to be related to the absence of one or more specific selenoproteins.14 Residents in seleniumrich areas tend to have healthy bodies. The reaction of selenium with reactive oxygen more readily takes place in vivo and is reversible even under mild oxidative conditions.15 Various reactions involving selenium are described as “easy in–easy out”. This is attributed to the strong nucleophilicity of se (...truncated)