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• W4295884794 endingPage "2203823" @default.
• W4295884794 startingPage "2203823" @default.
• W4295884794 abstract "Although small interfering RNA (siRNA) therapy has achieved great progress, unwanted gene inhibition in normal tissues severely limits its extensive clinical applications due to uncontrolled siRNA biodistribution. Herein, a spatially controlled siRNA activation strategy is developed to achieve tumor-specific siRNA therapy without gene inhibition in the normal tissues. The quaternary ammonium moieties are conjugated to amphiphilic copolymers via reactive oxygen species (ROS)-sensitive thioketal (TK) linkers for co-delivery of siRNA and photosensitizer chlorin e6 (Ce6), showing excellent siRNA complexation capacity and near infrared (NIR)-controlled siRNA release. In the normal tissue, siRNAs are trapped and degraded in the endo-lysosomes due to the unprotonatable property of quaternary ammonium moiety, showing the siRNA activity “off” state. When NIR irradiation is spatially applied to the tumor tissue, the NIR irradiation/Ce6-induced ROS trigger siRNA endo-lysosomal escape and cytosolic release through the photochemical internalization effect and cleavage of TK bonds, respectively, showing the siRNA activity “on” state. The siRNA-mediated glutathione peroxidase 4 gene inhibition enhances ROS accumulation. The synergistic antitumor activity of Ce6 photodynamic therapy and gene inhibition is confirmed in vivo. Spatially controlled tumor-specific siRNA activation and co-delivery with Ce6 using unprotonatable and ROS-sensitive cationic nanocarriers provide a feasible strategy for tumor-specific siRNA therapy with synergistic drug effects." @default.
• W4295884794 created "2022-09-16" @default.
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• W4295884794 date "2022-09-12" @default.
• W4295884794 modified "2023-10-02" @default.
• W4295884794 title "Unprotonatable and ROS‐Sensitive Nanocarrier for NIR Spatially Activated siRNA Therapy with Synergistic Drug Effect" @default.
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• W4295884794 doi "https://doi.org/10.1002/smll.202203823" @default.
• W4295884794 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36094800" @default.
• W4295884794 hasPublicationYear "2022" @default.
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