期刊
ANALYTICAL CHEMISTRY
卷 94, 期 2, 页码 811-819出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.1c03488
关键词
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资金
- National Natural Science Foundation of China [21405122, 21603174]
- Science and Technology Project of Yangling Demonstration Zone [2018SF-04]
- Natural Science Foundation of Shaanxi [2020JM-172]
A multifunctional photosensitizer was designed to be specifically activated by inflammatory cytokines and tumor markers, releasing a ratiometric fluorescence signal. This novel strategy showed promising results in the treatment of inflammation-associated tumors.
Inflammation exists in the microenvironment of most, if not virtually all, tumors, which greatly exacerbates the difficulty of cancer treatment. Considering the superiority of activatable photosensitizers (PSs), a novel strategy of 'making friends with the enemy' for tumor treatment was proposed. In this strategy, the enemy refers to inflammatory cytokines and the tumor site is targeted by detecting the enemy. Upon detection, a dichromatic fluorescence signal is released and the PS is activated specifically by the inflammatory cytokines. In this study, a multifunctional PS (TPE-PTZ-Py) was rationally designed, which can be activated specifically under the synergistic action of hypochlorous acid (HClO) (one kind of inflammatory cytokines) and acid (one typical marker of tumor), and output a ratiometric fluorescence signal simultaneously. The sulfoxide analogue (TPE-PTZO-PyH) as the response product effectively produced O-1(2) (1.8-fold higher than that obtained with Rose Bengal) and showed high phototoxicity (IC50 < 7.6 mu M). More importantly, imaging analyses confirmed that TPE-PTZ-Py could be activated in human cervical cancer tissue. To date, several phenothiazine (PTZ)-based fluorescent probes have been developed for the selective sensing and imaging of HClO in subcellular organelles; however, this is the first phenothiazine-based nanodrug designed for the treatment of inflammationassociated tumors with a few side effects.
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