Journal
NATURE CHEMISTRY
Volume 13, Issue 8, Pages 805-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41557-021-00711-4
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Funding
- ERC [ERC-2013-ADG 340469 ADREEM]
- National Natural Science Foundation of China [22071263, 22001261]
- Natural Science Foundation of Guangdong Province, China [2020A1515010994]
- Guangdong Province Zhujiang Talents Program [2019QN01Y127]
- Shenzhen Fundamental Research Program [JCYJ20200109110215774]
- 'Hundred Talents Program' of the Chinese Academy of Sciences
- China Postdoctoral Science Foundation [2020M672873, 2020M682976]
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The article introduces a chemistry-based strategy for simultaneous chemo-radiotherapy by activating cancer prodrugs through irradiation, enabling site-directed chemotherapy instead of systemic chemotherapy, which opens up a new era in targeted and directed chemotherapy.
Chemotherapy is a powerful tool in the armoury against cancer, but it is fraught with problems due to its global systemic toxicity. Here we report the proof of concept of a chemistry-based strategy, whereby gamma/X-ray irradiation mediates the activation of a cancer prodrug, thereby enabling simultaneous chemo-radiotherapy with radiotherapy locally activating a prodrug. In an initial demonstration, we show the activation of a fluorescent probe using this approach. Expanding on this, we show how sulfonyl azide- and phenyl azide-caged prodrugs of pazopanib and doxorubicin can be liberated using clinically relevant doses of ionizing radiation. This strategy is different to conventional chemo-radiotherapy radiation, where chemo-sensitization of the cancer takes place so that subsequent radiotherapy is more effective. This approach could enable site-directed chemotherapy, rather than systemic chemotherapy, with 'real time' drug decaging at the tumour site. As such, it opens up a new era in targeted and directed chemotherapy.
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