Theranostic Gold Nanoparticles Modified for Durable Systemic Circulation Effectively and Safely Enhance the Radiation Therapy of Human Sarcoma Cells and Tumors |
| |
Authors: | Daniel Y Joh Gary D Kao Surya Murty Melissa Stangl Lova Sun Ajlan Al Zaki Xiangsheng Xu Stephen M Hahn Andrew Tsourkas Jay F Dorsey |
| |
Institution: | 2. Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA |
| |
Abstract: | Radiation therapy (RT) is an integral component of the treatment of many sarcomas and relies on accurate targeting of tumor tissue. Despite conventional treatment planning and RT, local failure rates of 10% to 28% at 5 years have been reported for locally advanced, unresectable sarcomas, due in part to limitations in the cumulative RT dose that may be safely delivered. We describe studies of the potential usefulness of gold nanoparticles modified for durable systemic circulation (through polyethylene glycosylation; hereinafter “P-GNPs”) as adjuvants for RT of sarcomas. In studies of two human sarcoma-derived cell lines, P-GNP in conjunction with RT caused increased unrepaired DNA damage, reflected by approximately 1.61-fold increase in γ-H2AX (histone phosphorylated on Ser139) foci density compared with RT alone. The combined RT and P-GNP also led to significantly reduced clonogenic survival of tumor cells, compared to RT alone, with dose-enhancement ratios of 1.08 to 1.16. In mice engrafted with human sarcoma tumor cells, the P-GNP selectively accumulated in the tumor and enabled durable imaging, potentially aiding radiosensitization as well as treatment planning. Mice pretreated with P-GNP before targeted RT of their tumors exhibited significantly improved tumor regression and overall survival, with long-term survival in one third of mice in this treatment group compared to none with RT only. Interestingly, prior RT of sarcoma tumors increased subsequent extravasation and in-tumor deposition of P-GNP. These results together suggest P-GNP may be integrated into the RT of sarcomas, potentially improving target imaging and radiosensitization of tumor while minimizing dose to normal tissues. |
| |
Keywords: | |
本文献已被 ScienceDirect 等数据库收录! |
|