Abstract

Radiotherapy (RT), in combination with surgery, is an essential treatment strategy for oral cancer. Although irradiation provides effective control over tumor growth, the surrounding normal tissues are almost inevitably affected. With further understanding of the molecular mechanisms involved in radiation response and recent advances in nanotechnology, using gold nanoparticles as a radiosensitizer provides the preferential sensitization of tumor cells to radiation and minimizes normal tissue damage. Herein, we developed gold nano-sesame-beads (GNSbs), a gold-nanorod-seeded mesoporous silica nanoparticle, as a novel radioenhancer to achieve radiotherapy with a higher therapeutic index. GNSbs in combination with 2 Gy irradiation effectively enhanced the cytotoxic activity CAL-27 cells. The well-designed structure of GNSbs showed preferential cellular uptake by CAL-27 cells at 24 h after incubation. Gold nanorods with high density modified on mesoporous silica nanoparticles resulted in significant reactive oxygen species (ROS) formation after irradiation exposure compared with irradiation alone. Furthermore, GNSbs and irradiation induced more prominent DNA double-strand breaks and G2/M phase arrest in CAL-27 than those in L929. In animal studies, radiotherapy using GNSbs as a radiosensitizer showed significant suppression of tumor growth in an orthotopic model of oral cancer. These results demonstrate that using GNSbs as a radiosensitizer could possess clinical potential for the treatment of oral squamous carcinoma.

Highlights

  • The monodispersed mesoporous silica nanobeads had an average size of 140 ± 20 nm with homogenously distributed columnar pores of 7 ± 2 nm

  • Evenly distributed gold nanorods in mesoporous silica were synthesized (Figure 1d,g) in situ by this seed-mediated growth process in the channels of silica nanobeads, which confines the diameter of gold nanorods to a hard silica template

  • New gold nano-sesame-beads (GNSbs) of mesoporous silica nanobeads with pores filled with gold nanorods were successfully developed

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Summary

Introduction

More than 500,000 new cases of head and neck cancer are diagnosed worldwide each year. This represents an important global health problem [1]. Head and neck cancer commonly develop in the oral cavity. Squamous cell carcinoma is the most common pathological type in oral cancer [2]. Radiation therapy has a vital role in current treatment strategies for oral squamous cell carcinoma. Major improvements in the treatment of oral squamous cell carcinoma have been accomplished by combining sophisticated surgical techniques and radiotherapy (RT) delivery [3]. There are several inevitable complications caused by radiotherapy, such as mucositis, osteoradionecrosis, radiation caries, etc. Oral mucositis can occur in most patients

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