RGD-conjugated gold nanorods induce radiosensitization in melanoma cancer cells by downregulating α_vβ₃ expression

Wencai Xu¹, Teng Luo², Ping Li¹, Chuanqing Zhou², Daxiang Cui³, Bo Pang⁴, Qiushi Ren⁴, Shen Fu<sup>1

1</sup>Department of Radiation Oncology, Shanghai Sixth People's Hospital, ²School of Biomedical Engineering, and ³National Key Laboratory of Nano/Micro Fabrication Technology, Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Institute of Micro-Nano Science and Technology, Shanghai Jiao Tong University, Shanghai, ⁴Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, People's Republic of China

Background: Melanoma is known to be radioresistant and traditional treatments have been intractable. Therefore, novel approaches are required to improve the therapeutic efficacy of melanoma treatment. In our study, gold nanorods conjugated with Arg-Gly-Asp peptides (RGD-GNRs) were used as a sensitizer to enhance the response of melanoma cells to 6 mV radiation.
Methods and materials: A375 melanoma cells were treated by gold nanorods or RGD-GNRs with or without irradiation. The antiproliferative impact of the treatments was measured by MTT assay. Radiosensitizing effects were determined by colony formation assay. Apoptosis and cell cycle data were measured by flow cytometry. Integrin α_vβ₃expression was also investigated by flow cytometry.
Results: Addition of RGD-GNRs enhanced the radiosensitivity of A375 cells with a dose-modifying factor of 1.35, and enhanced radiation-induced apoptosis. DNA flow cytometric analysis indicated that RGD-GNRs plus irradiation induced significant G2/M phase arrest in A375 cells. Both spontaneous and radiation-induced expressions of integrin α_vβ₃ were downregulated by RGD-GNRs.
Conclusion: Our study indicated that RGD-GNRs could sensitize melanoma A375 cells to irradiation. It was hypothesized that this was mainly through downregulation of radiation-induced α_vβ₃, in addition to induction of a higher proportion of cells within the G2/M phase. The combination of RGD-GNRs and radiation needs further investigation.

Keywords: radiosensitivity, melanoma, Arg-Gly-Asp peptides, gold nanorods, integrin α_vβ₃, G2/M arrest
 

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