Research Article
Enhancement of cell permeabilization apoptosis-inducing activity of selenium nanoparticles by ATP surface decoration

https://doi.org/10.1016/j.nano.2012.04.002Get rights and content

Abstract

A simple method for preparation of adenosine triphosphate (ATP) surface-functionalized selenium nanoparticles (SeNPs@ATP) with enhanced cell permeabilization and anticancer activity has been demonstrated in the study reported in this article. Spherical SeNPs were decorated with ATP by strong adsorption through an Se-N bond, leading to the highly stable structure of the conjugates. ATP surface decoration significantly enhanced the cellular uptake and anticancer activity of SeNPs. Induction of apoptosis in HepG2 human hepatocellular carcinoma cells by SeNPs@ATP was evidenced by accumulation of the sub-G1 cell population, phosphatidylserine exposure, DNA fragmentation, PARP cleavage and caspase activation. Further studies found that SeNPs@ATP treatment triggered the depletion of mitochondrial membrane potential and reactive oxygen species (ROS) overproduction. Our results demonstrate that the use of ATP as a surface decorator of SeNPs is a novel strategy to achieve anticancer synergy. SeNPs@ATP may be a candidate for further evaluation as a chemotherapeutic agent for human cancers.

From the Clinical Editor

In this paper, adenosine triphosphate (ATP) surface-functionalized selenium nanoparticles are discussed as cell-penetrating anticancer agents. Conjugates are stable and ATP functionalization greatly enhances the apoptosis induction properties of the selenium nanoparticles in HepG2 human hepatocellular carcinoma cells.

Graphical abstract

ATP surface decoration significantly enhances the cellular uptake and anticancer activity of SeNPs. Induction of apoptosis was the major mode of cancer cell death induced by SeNPs@ATP. Our results demonstrate that it is a novel strategy to use ATP as a surface decorator of SeNPs to achieve anticancer synergism. SeNPs@ATP may be a candidate for further evaluation as a therapeutic agent for human cancers.

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Section snippets

Preparation of SeNPs@ATP

Aqueous ATP (Sigma-Aldrich, St. Louis, Missouri) solution (50 mM, 4 ml) was mixed with 2 mL 100 mM ascorbic acid (Sigma-Aldrich) and 13.5 mL Milli-Q water under magnetic stirring. Aqueous sodium selenite (Sigma-Aldrich) solution (40 mM, 0.5 ml) was slowly added into the mixtures. After reaction for 5 minutes under sonication, the solutions were dialyzed against Milli-Q water at 4°C until no Se was detected in the outer solutions as determined by ICP-AES (Inductively Coupled Plasma-Atomic

Preparation and characterization of SeNPs@ATP

This article summarizes the present study, in which we demonstrated a simple method to synthesize functionalized SeNPs through conjugation of ATP to the surface of Se nanoparticles. Figure 1 shows the representative TEM images of the as-prepared SeNPs with the absence (A) and presence (B) of 10 mM ATP, which clearly revealed that SeNPs@ATP presented monodisperse and homogeneous spherical structure with an average diameter of about 40 nm, whereas SeNPs alone in aqueous solutions were badly

Discussion

The development of cancer-nanotechnology has opened the new horizons for cancer imaging, diagnosis, and targeted therapy.1, 2, 29 Numerous nanomaterials have been applied in cancer imaging, diagnosis, and therapy due to their unique optical, magnetic, radiological, and structural properties.1, 2, 4, 29, 30, 31 For instance, great achievements have been made by using nanoscale liposomes to deliver Zoledronic acid.32, 33, 34, 35 Carbon nanotubes have also been proved to be an excellent drug

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      Citation Excerpt :

      Recently, selenium nanoparticles (SeNPs) have appeared to be more effective in increasing selenoprotein levels than other forms of selenium. Numerous surface modification methods, such as capping via ATP or vitamin C, were introduced as effective strategies to enhance the stability, cellular uptake, and size control of SeNPs [156]. To further potentiate SeNPs as IBD attenuating materials, Zhu et al. decorated the surface of SeNPs with ulca lactuca polysaccharide, a material known to possess immunomodulatory, antioxidant, and surfactant properties [157,158].

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    No conflict of interest was reported by the authors of this paper.

    This work was supported by Natural Science Foundation of China and Guangdong Province, Program for New Century Excellent Talents in University, Key Project of Science and Technology Department of Guangdong Province, the Fundamental Research Funds for the Central Universities and Grant of State Key Laboratory of Oncology in South China.

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