Superoxide Radical Photogenerator with Amplification Effect: Surmounting the Achilles’ Heels of Photodynamic Oncotherapy
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- 17 January 2019
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 141 (6), 2695-2702
- https://doi.org/10.1021/jacs.8b13141
Abstract
Strong oxygen dependence, poor tumor targeting, and limited treatment depth have been considered as the “Achilles’ heels” facing the clinical usage of photodynamic therapy (PDT). Different from common approaches, here, we propose an innovative tactic by using photon-initiated dyad cationic superoxide radical (O2−•) generator (ENBOS) featuring “0 + 1 > 1” amplification effect to simultaneously overcome these drawbacks. In particular, by taking advantage of the Förster resonance energy transfer theory, the energy donor successfully endows ENBOS with significantly enhanced NIR absorbance and photon utility, which in turn lead to ENBOS more easily activated and generating more O2−• in deep tissues, thus dramatically intensifies the type I PDT against hypoxic deep tumors. Moreover, benefiting from the dyad cationic feature, ENBOS achieves superior “structure-inherent targeting” abilities with the signal-to-background ratio as high as 25.2 at 48 h post intravenous injection, offering opportunities for accurate imaging-guided tumor treatment. Meanwhile, the intratumoral accumulation and retention performance are also markedly improved (> 120 h). Based on these unique merits, ENBOS selectively inhibits the deep-seated hypoxic tumor proliferation at a low light-dose irradiation. Therefore, this delicate design may open up new horizons and cause a paradigm change for PDT in future cancer therapy.Keywords
Funding Information
- National Natural Science Foundation of China (21421005, U1608222, 21576037)
- Liaoning Province (U1608222)
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