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Theranostics 2016; 6(13):2295-2305. doi:10.7150/thno.16141 This issue Cite

Research Paper

X-Ray Induced Photodynamic Therapy: A Combination of Radiotherapy and Photodynamic Therapy

Geoffrey D. Wang^1*, Ha T. Nguyen^2*, Hongmin Chen^1✉, Phillip B. Cox³, Lianchun Wang⁴, Koichi Nagata⁵, Zhonglin Hao⁶, Andrew Wang⁷, Zibo Li⁸, Jin Xie^1✉

1. Department of Chemistry, Bio-Imaging Research Center, the University of Georgia, Athens, Georgia 30602, USA;
2. National Exposure Research Lab, US Environmental Protection Agency, Athens, Georgia 30605, USA;
3. Department of Cellular Biology, the University of Georgia, Athens, Georgia 30602, USA;
4. Department of Biochemistry and Molecular Biology, the University of Georgia, Athens, Georgia 30602, USA;
5. College of Veterinary Medicine, The University of Georgia, Athens, GA 30602, USA;
6. Section of Hematology and Oncology, Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, Georgia 30912, USA;
7. Laboratory of Nano- and Translational Medicine, Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, University of North Carolina at Chapel Hill, Chapel Hill, USA;
8. Department of Radiology and Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
*Equal contribution

✉ Corresponding author: hchenedu Or jinxieedu.

Abstract

Conventional photodynamic therapy (PDT)'s clinical application is limited by depth of penetration by light. To address the issue, we have recently developed X-ray induced photodynamic therapy (X-PDT) which utilizes X-ray as an energy source to activate a PDT process. In addition to breaking the shallow tissue penetration dogma, our studies found more efficient tumor cell killing with X-PDT than with radiotherapy (RT) alone. The mechanisms behind the cytotoxicity, however, have not been elucidated. In the present study, we investigate the mechanisms of action of X-PDT on cancer cells. Our results demonstrate that X-PDT is more than just a PDT derivative but is essentially a PDT and RT combination. The two modalities target different cellular components (cell membrane and DNA, respectively), leading to enhanced therapy effects. As a result, X-PDT not only reduces short-term viability of cancer cells but also their clonogenecity in the long-run. From this perspective, X-PDT can also be viewed as a unique radiosensitizing method, and as such it affords clear advantages over RT in tumor therapy, especially for radioresistant cells. This is demonstrated not only in vitro but also in vivo with H1299 tumors that were either subcutaneously inoculated or implanted into the lung of mice. These findings and advances are of great importance to the developments of X-PDT as a novel treatment modality against cancer.

Keywords: photodynamic therapy, radiotherapy, lung cancer, clonogenecity, nanoparticles.

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