PEG-nanolized ultrasmall selenium nanoparticles overcome drug resistance in hepatocellular carcinoma HepG2 cells through induction of mitochondria dysfunction

Abstract

Gray selenium (Se) is one of the most widely used Se sources with very limited biocompatibility and bioactivity. In the present study, a simple method for the preparation of ultrasmall selenium nanoparticles (SeNPs) through direct nanolization of gray selenium by polyethylene glycol (PEG) was demonstrated. Monodisperse and homogeneous PEG-SeNPs with ultrasmall diameters were successfully prepared under optimized conditions. The products were characterized using various microscopic and spectroscopic methods, and the results suggest that the amphoteric properties of PEG and the coordination between oxygen and selenium atoms contributed to the formation of ultrasmall nanoparticles. PEG-SeNPs exhibited stronger growth inhibition on drug-resistant hepatocellular carcinoma (R-HepG2) cells than on normal HepG2 cells. Dose-dependent apoptosis was induced by PEG-SeNPs in R-HepG2 cells, as evidenced by an increase in the sub-G1 cell population. Further investigation on the underlying molecular mechanisms revealed that depletion of mitochondrial membrane potential and generation of superoxide anions contributed to PEG-SeNPs-induced apoptotic cell death in R-HepG2 cells. Our results suggest that PEG-SeNPs may be a candidate for further evaluation as a chemotherapeutic agent for drug-resistant liver cancer, and the strategy to use PEG200 as a surface decorator could be a highly efficient way to enhance the anticancer efficacy of nanomaterials.

Cerebrospinal fluid of newly diagnosed amyotrophic lateral sclerosis patients exhibits abnormal levels of selenium species including elevated selenite

“…Inorganic Se forms and selenite in particular are well recognized in laboratory studies to be considerably more toxic than organic species (Benko et al, 2012; Peyroche et al, 2012; Vinceti et al, 2013), particularly for neurotoxic effects (Ammar and Couri, 1981; Tsunoda et al, 2000), even though they are retained in humans (Thomson et al, 1993) and animals (Vinceti et al, 2009) at a considerably lower rate than organic compounds. Selenite, and other Se species (Zheng et al, 2012), can induce oxidative stress and mitochondrial damage (Belyaeva and Saris, 2011; Ma et al, 2011), and both free radical damage and mitochondrial abnormalities have been implicated in ALS etiopathogenesis (Rossi et al, 2012). Selenite in vitro has also been shown to induce other biochemical alterations suggested to occur in ALS, such as copper/zinc superoxide-dismutase (SOD1) translocation into mitochondria and increased levels of reactive oxygen species and of inducible nitric oxide synthase, with enhanced susceptibility to Se toxicity by nervous cells compared with other cell types (Maraldi et al, 2011).…”

The Advancing of Selenium Nanoparticles Against Infectious Diseases

“…Se NPs can be formed from selenium element in the guidence of some chemical templates as stabilizers. PEG200 was introduced as a kind of template and surface decorator for Se NPs synthesis (Zheng et al, 2012). Firstly, gray Se was dissolved in PEG200 solution at 210-220°C for 15-20 min, followed the addtion of water at a ratio of 1:1.…”

Recent Advances in Chemical Biology of Mitochondria Targeting

“…PEG-SeNCs exhibited stronger growth inhibition and induced concentration-dependent apoptosis to the drug-resistant hepatocellular carcinoma (R-HepG2) cells. Further molecular investigation revealed that the anti-cancer effect was due to the depletion of mitochondrial membrane potential and generation of superoxide anions ( Zheng et al, 2012 ). Tan et al created a PCL-based mitochondria-targeting DDS, by using TPP + as mitochondria-targeting molecule.…”

“…(B) Schematic diagram of a PEG-coated selenium cluster. Image reproduced with permission, from Ref Zheng et al (2012) . (C) The chemical structure of a mitochondria-targeting co-polymer with TPP + side chains.…”