Molecular Engineering To Accelerate Cancer Cell Discrimination And Boost Aie-Active Type I Photosensitizer For Photodynamic Therapy Under Hypoxia
CHEMICAL ENGINEERING JOURNAL(2021)
Abstract
The severe hypoxia in solid tumor and the accurate discrimination between cancer and normal cells gravely restrict the application of fluorescence imaging-guided photodynamic therapy (PDT), although this cancer-therapy modality has significant superiorities in terms of precise visualization of the location of photosensitizers (PSs) in tumor tissue as well as noninvasive and reliable treatment. A convenient and universal fluorescence system featuring Type I reactive oxygen species (ROS) based on free radicals, wide-spectrum cancer cell discrimination and distinctive aggregation-induced emission (AIE) characteristics could offer a feasible approach to resolve the problems above, which is yet extremely challenging. Herein, we propose a series of electron-rich anion-pi(+) AIE-active luminogens (AIEgens) fabricating increasingly stronger intermolecular charge transfer (ICT) state to promote highly efficient intersystem crossing for boosting Type I ROS generation. Moreover, MeOTPPM has priority to enter cancer cells with better plasma membrane permeability due to the strongest binding force with water molecules. This work serves as a pioneering reference for rationally constructing Type I-based purely organic PSs to overcome tumor hypoxia defects in PDT and selectively targeting and ablating cancer cells over normal cells without the aid of any extra cancer cell-specific targeting ligands.
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Key words
Molecular design, AIEgens, Type I ROS, Cancer cell discrimination, Photodynamic therapy
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