期刊
THERANOSTICS
卷 6, 期 13, 页码 2295-2305出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.16141
关键词
photodynamic therapy; radiotherapy; lung cancer; clonogenecity; nanoparticles
资金
- DoD CDMRP grant [CA140666]
- NSF CAREER grant [NSF1552617]
- UGA-GRU seed grant
- NIH P41 grant [GM103390]
- Direct For Mathematical & Physical Scien
- Division Of Materials Research [1552617] Funding Source: National Science Foundation
- CDMRP [793849, CA140666] Funding Source: Federal RePORTER
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.
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