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A de novo zwitterionic strategy of ultra-stable chemiluminescent probes: highly selective sensing of singlet oxygen in FDA-approved phototherapy.


ABSTRACT: Singlet oxygen (1O2), as a fundamental hallmark in photodynamic therapy (PDT), enables ground-breaking clinical treatment in ablating tumors and killing germs. However, accurate in vivo monitoring of 1O2 remains a significant challenge in probe design, with primary difficulties arising from inherent photo-induced side reactions with poor selectivity. Herein, we report a generalizable zwitterionic strategy for ultra-stable near-infrared (NIR) chemiluminescent probes that ensure a highly specific [2 + 2] cycloaddition between fragile electron-rich enolether units and 1O2 in both cellular and dynamic in vivo domains. Innovatively, zwitterionic chemiluminescence (CL) probes undergo a conversion into an inert ketone excited state with an extremely short lifetime through conical intersection (CI), thereby affording sufficient photostability and suppressing undesired photoreactions. Remarkably, compared with the well-known commercial 1O2 probe SOSG, the zwitterionic probe QMI exhibited an ultra-high signal-to-noise ratio (SNR, over 40-fold). Of particular significance is that the zwitterionic CL probes demonstrate excellent selectivity, high sensitivity, and outstanding photostability, thereby making a breakthrough in real-time tracking of the FDA-approved 5-ALA-mediated in vivo PDT process in living mice. This innovative zwitterionic strategy paves a new pathway for high-performance NIR chemiluminescent probes and high-fidelity feedback on 1O2 for future biological and medical applications.

SUBMITTER: Lu Y 

PROVIDER: S-EPMC11304548 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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A <i>de novo</i> zwitterionic strategy of ultra-stable chemiluminescent probes: highly selective sensing of singlet oxygen in FDA-approved phototherapy.

Lu Yao Y   Zhang Yutao Y   Wu Xia X   Pu Ruihua R   Yan Chenxu C   Liu Weimin W   Liu Xiaogang X   Guo Zhiqian Z   Zhu Wei-Hong WH  

Chemical science 20240624 31


Singlet oxygen (<sup>1</sup>O<sub>2</sub>), as a fundamental hallmark in photodynamic therapy (PDT), enables ground-breaking clinical treatment in ablating tumors and killing germs. However, accurate <i>in vivo</i> monitoring of <sup>1</sup>O<sub>2</sub> remains a significant challenge in probe design, with primary difficulties arising from inherent photo-induced side reactions with poor selectivity. Herein, we report a generalizable zwitterionic strategy for ultra-stable near-infrared (NIR) che  ...[more]

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