(220b) Effects of Red Allotrope Selenium Nanoparticles on Head and Neck Squamous Cell Carcinoma

Authors: 
Webster, T. J., Northeastern University

Effect of Red Selenium Nanoparticles on Head and Neck Squamous Cell Carcinoma

Christopher Hassan1 and Thomas J Webster1,2

1Department of Chemical Engineering, Northeastern University, Boston, MA, USA

2Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia

Statement of Purpose: With approximately 540,000 new cases occurring annually worldwide, a mortality rate of fifty percent, head and neck squamous cell carcinoma (HNSCC) continues to be an extremely difficult cancer to treat, let alone cure. Though patients in the United States tend to receive the best forms of treatment available, survival rates remain low at less than five years,[1] with locoregional reoccurrence being quite common.[2] The disease is most commonly found in middle-aged men who have histories of heavy smoking or tobacco usage and excessive alcohol consumption. However, recent studies have shown that it has an unusually high rate of occurrence in young women, many of whom have had no obvious risk factors, though a possible causal link between HNSCC and human papillomavirus (HPV) has been observed. Genetic analysis of the disease has shown the most likely causes to be tumor suppressor gene inactivation and overexpression of several proto-oncogenes, particularly p53,1 which regulates cell proliferation via induction of apoptosis. Surgical treatments are available, but the fact that HNSCC occurs in the neck limits the depth to which surgeons can cut, with the additional problem that any immunogenic inflammatory response would cause significant airway obstruction.[3]

In recent years, studies have found selenium to be capable of selectively targeting cells expressing mutated p53 or lacking p53, while simultaneously modulating DNA repair in cells with wild type p53 expression. When delivered to the body in supplementary form, this has been shown to allow for higher tolerable doses of chemotherapeutic medications.[4] Additionally, when coupled covalently to polyethylene glycol (PEG), a nanoparticle anti-aggregate, selenium nanoparticles are capable of inducing apoptosis in drug-resistant cancers cells through the destabilization of the mitochondrial membrane potential.[5]Selenium nanoparticles have therefore been deemed a viable candidate for study of their effect on HNSCC.

Methods:Red selenium nanoparticles were made in lab via the mixing of sodium selenite and glutathione in an alkali environment and were characterized to be 100nm in diameter and have surface charges of -22.05mV .

Viability tests were performed on human dermal fibroblasts (HDF) and head and neck squamous cell carcinoma (SCC-9) cell lines. HDF and SCC-9 were both obtained from ATCC. HDF was cultured in Dulbecco’s Modified Eagle Medium (DMEM), supplemented with 10% fetal bovine serum (FBS), and 1% antibiotic-antimycotic (anti-anti), from 7 to 10 cell passage numbers. SCC-9 was cultured in a 1:1 mixture of DMEM and Ham’s F-12 Nutrient Mixture (DMEM:F-12) supplemented with 10% FBS, 1% anti-anti, and 50mg/mL hydrocortisone, from 2 to 5 cell passage numbers. Viability assays were performed for 1, 2, and 3 days, with MTS used at the viability indicator.

Results:Results indicated a capacity for red selenium nanoparticles to induces apoptosis in HNSCC cells at concentrations of 50 to 100μg/mL after three days, while minimizing damage to surrounding fibroblasts.

Conclusions:The in vitro treatment of HNSCC with red selenium nanoparticles displayed promising effectiveness, while simultaneously minimizing cytotoxicity of dermal fibroblasts. Further studies will be conducted to fully characterize the nanoparticles. The particles will also be functionalized with PEG to allow for decreased agglomeration while in solution. The viability of these functionalized particles will be analyzed as well. Furthermore, in-depth analysis of the transport of selenium nanoparticles into the cells and the effect of the particles on intracellular superoxide generation and mitochondrial membrane potential destabilization will be performed to determine the exact method by which the particles effect the cells.

Acknowledgments: The authors thank Northeastern University for funding.




References:

[1] Perez-Ordonez, B, M Beauchemin, and R C K Jordan. Molecular Biology of Squamous Cell Carcinoma of the Head and Neck. Journal of Clinical Pathology, 2006, 59, 445 – 453.

[2] Koch, Wayne M., et al. p53 Mutation and Locoregional Treatment Failure in Head and Neck Squamous Cell Carcinoma. Journal of the National Cancer Institute, Nov 6, 1996, 88(21), 1580 – 1586.

[3] Pirollo, Kathleen F, et al. p53 Mediated Sensitization of Squamous Cell Carcinoma of the Head and Neck to Radiotherapy. Oncogene, 1997, 14, 1735 – 1746.

[4] Fischer, Joshua L, et al. Chemotherapeutic Selectivity Conferred by Selenium: A Role for p53-Dependent DNA Repair. Molecular Cancer Therapeutics, 2007, 6, 355 – 361.

[5] Zheng, Shanyuan, et al. PEG-Nanolized Ultrasmall Selenium Nanoparticles Overcome Drug Resistance in Heptocellular Carcinoma HepG2 Cells Through Induction of Mitochondrian Dysfunction. International Journal of Nanomedicine, 2012, 7, 3939 – 3949.

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