Induction of apoptosis by high-dose gold nanoparticles in nasopharyngeal carcinoma cells
Introduction
Nasopharyngeal carcinoma (NPC) is a rare malignancy in most parts of the world, but is one of the most common cancers among Chinese or Asian ancestry. Its annual incidence in southern China is >20 cases per 100,000, which is much higher compared to other populations not as risk [1]. Its etiology is thought to be associated with a complex interaction of genetic, environmental and dietary factors, as well as Epstein–Barr virus exposure. Definitive diagnosis is made by biopsy of the nasopharyngeal tumor under direct visualization with the endoscope. However, NPC is often diagnosed late due to its deep location and vague symptoms, such that 60–70% of cases present with neck lymph node metastasis, and 5–11% of these present with distant metastasis [2].
Radiotherapy is the foundation of curative treatment although chemotherapy has been used in cases with advanced stages. However, advanced NPC patients who have concurrent chemoradiation therapy often suffer from radiation- or chemotherapy-related complications [2]. Contemporary NPC research, including genomics, proteomics, metabolomics and bioinformatics, has unraveled possible molecular mechanisms of this malignancy, and many molecular biomarkers have been discovered, enabling the development of specific molecular targeted therapies as potential therapeutic agents [1], [3], [4], [5].
Nanotechnology has engendered a range of novel materials with unique properties and raised the possibility of designing molecularly targeted therapeutic or diagnostic agents. Nanoparticles can be effectively endocytosed by the cells, resulting in a high cellular uptake of entrapped biomarkers or therapeutic agents. Gold nanoparticles (AuNPs) have distinct advantages due to their relatively high biocompatibility, photo-stability, and ease of conjugation to biomolecules [6].
Recently, AuNPs have been developed as potential in vivo diagnostic and therapeutic agents, as X-ray contrast agents, drug delivery vehicles and radiation enhancers [7]. Although several studies have shown that AuNPs conjugated with certain biomolecules or drugs are potent against some cancer cell lines like prostate cancer [8], [9] and ovarian cancer [10], their role on nasopharyngeal cancer remains unknown. The present study investigated whether or not AuNPs have cytotoxic effects on NPC cells in vitro.
Section snippets
Preparation of AuNPs
AuNPs were prepared by the reduction of chloroauric acid (Au3+, HAuCl4) to neutral gold (Au0) by sodium citrate. Briefly, water solutions of hydrogen tetrachloroaurate trihydrate and trisodium citrate dihydrate were mixed under heavy boiling, resulting in gold particles with a net negative charge from the citrate ions, which stabilized the particles. Varying the citrate to HAuCl4 concentration ratio produced particles with an average size of about 20.5 nm. The AuNPs formed were then filtered
Results
The TEM image of the prepared AuNPs showed the size of the nanoparticles followed a normal distribution with an average diameter of 20.5 nm and standard deviation of 6.8 nm. The inset showed the corresponding diffraction pattern, which identified these nanoparticles to be composed of gold (Fig. 1A). The AuNPs were also characterized by an absorption maximum at 527 nm with a full width at half-maximum of approximately 58 nm (Fig. 1B). AuNPs aggregated in the cells probably via endocytosis and were
Discussion
Targeted metallic nanoparticles have been shown to be promising contrast agents for molecular imaging [11]. AuNPs provide strong contrast based on their unique optical absorption and scattering properties [6]. Studies by Sokolov et al. and El-Sayed et al. have demonstrated AuNPs to be useful for molecular bio-sensing and imaging with white light source due to their strong ability to absorb and scatter light in the visible region of the spectrum [12], [13]. They have used AuNPs to image receptor
Conclusion
The AuNPs possess specific imaging properties and are cytotoxic to NPC cells at high concentrations. Their potential use in the treatment of NPC merits further studies.
Conflict of interest
No potential conflicts of interest were disclosed.
Acknowledgments
This work was supported by a grant from the Veterans General Hospitals University System of Taiwan Joint Research Program (VGHUST98-DHA-0500004).
References (36)
- et al.
Pancreatic carcinoma cells are susceptible to noninvasive radio frequency fields after treatment with targeted gold nanoparticles
Surgery
(2010) - et al.
A gold nanoparticle platform for the delivery of function microRNAs into cancer al cells
Biomaterials
(2013) - et al.
Autophagy and oxidative stress associated with gold nanoparticles
Biomaterials
(2010) - et al.
Genomic instability of gold nanoparticle treated human lung fibroblast cells
Biomaterials
(2011) - et al.
Selective laser photo-thermal therapy of epithelial carcinoma using anti-EGFR antibody conjugated gold nanoparticles
Cancer Lett
(2006) - et al.
Use of tumor necrosis factor-alpha-coated gold nanoparticles to enhance radiofrequency ablation in a translational model of renal tumors
Urology
(2010) Nasopharyngeal carcinoma: molecular biomarker discovery and progress
Mol Cancer
(2007)- et al.
Neoplasms of the nasopharynx
- et al.
From NPC therapeutic target identification to potential treatment strategy
Mol Cancer Ther
(2010) - et al.
Nasopharyngeal carcinoma: molecular pathogenesis and therapeutic developments
Expert Rev Mol Med
(2007)