Journal
SMALL
Volume 12, Issue 29, Pages 3967-3975Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.201601375
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Funding
- National Basic Research Programs of China (973 Program) [2012CB932600]
- National Natural Science Foundation of China [51525203, 51572180, 81471716, 31400861]
- Juangsu Natural Science Fund [BK20130005, BK20140320]
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions
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Radioisotope therapy (RIT), in which radioactive agents are administered or implanted into the body to irradiate tumors from the inside, is a clinically adopted cancer treatment method but still needs improvement to enhance its performances. Herein, it is found that polyethylene glycol (PEG) modified tungsten disulfide (WS2) nanoflakes can be easily labeled by Re-188, a widely used radioisotope for RIT, upon simple mixing. Like other high-Z elements acting as radiosensitizers, tungsten in the obtained Re-188-WS2-PEG would be able to absorb ionization radiation generated from Re-188, enabling self-sensitization to enhance the efficacy of RIT as demonstrated in carefully designed in vitro experiments of this study. In the meanwhile, the strong NIR absorbance of WS2-PEG could be utilized for NIR light-induced photothermal therapy (PTT), which if applied on tumors would be able to greatly relieve their hypoxia state and help to overcome hypoxia-associated radioresistance of tumors. Therefore, with Re-188-WS2-PEG as a multifunctional agent, which shows efficient passive tumor homing after intravenous injection, in vivo self-sensitized, NIR-enhanced RIT cancer treatment is realized, achieving excellent tumor killing efficacy in a mouse tumor model. This work presents a new concept of applying nanotechnology in RIT, by delivering radioisotopes into tumors, self-sensitizing the irradiation-induced cell damage, and modulating the tumor hypoxia state to further enhance the therapeutic outcomes.
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