Cytosolic NQO1 Enzyme-Activated Near-Infrared Fluorescence Imaging and Photodynamic Therapy with Polymeric Vesicles
journal contributionposted on 2020-01-21, 13:34 authored by Chenzhi Yao, Yamin Li, Zhixiong Wang, Chengzhou Song, Xianglong Hu, Shiyong Liu
The utilization of enzymes as a triggering module could endow responsive polymeric nanostructures with selectivity in a site-specific manner. On the basis of the fact that endogenous NAD(P)H:quinone oxidoreductase isozyme 1 (NQO1) is overexpressed in many types of tumors, we report on the fabrication of photosensitizer-conjugated polymeric vesicles, exhibiting synergistic NQO1-triggered turn-on of both near-infrared (NIR) fluorescence emission and a photodynamic therapy (PDT) module. For vesicles self-assembled from amphiphilic block copolymers containing quinone trimethyl lock-capped self-immolative side linkages and quinone-bridged photosensitizers (coumarin and Nile blue) in the hydrophobic block, both fluorescence emission and PDT potency are initially in the “off” state due to “double quenching” effects, that is, dye-aggregation-caused quenching and quinone-rendered PET (photoinduced electron transfer) quenching. After internalization into NQO1-positive vesicles, the cytosolic NQO1 enzyme triggers self-immolative cleavage of quinone linkages and fluorogenic release of conjugated photosensitizers, leading to NIR fluorescence emission turn-on and activated PDT. This process is accompanied by the transformation of vesicles into cross-linked micelles with hydrophilic cores and smaller sizes and triggered dual drug release, which could be directly monitored by enhanced magnetic resonance (MR) imaging for vesicles conjugated with a DOTA(Gd) complex in the hydrophobic bilayer. We further demonstrate that the above strategy could be successfully applied for activated NIR fluorescence imaging and tissue-specific PDT under both cellular and in vivo conditions.
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NADNIR fluorescence imagingreleasephotoinduced electron transfermodulequenchingNIR fluorescence emission turn-onquinone trimethyl lock-capped self-immolative side linkagesDOTAfluorescence emissionMRphotosensitizerNQO 1-positive vesiclesPDTCytosolic NQO 1 Enzyme-Activated Near-Infrared Fluorescence ImagingNQO 1-triggered turn-onamphiphilic block copolymerscytosolic NQO 1 enzyme triggers self-immolative cleavage