2026/03/01 by Chao Zhao, Xinlan Lai, Yu Zhang (12946) +4 · 1 voice · 1 citation
Engineering · Medicine · #Nanoplatforms for cancer theranostics #Photoacoustic and Ultrasonic Imaging #Photodynamic Therapy Research Studies
paper · doi:10.1002/agt2.70300
openalex publication_date 2026/03/01 · openalex created_date 2026/03/06 · openalex updated_date 2026/08/01
ABSTRACT The single‐locked photosensitizers (PSs) still suffer from off‐target activation and skin phototoxicity in photodynamic therapy (PDT). Moreover, the efficacy of PDT is significantly limited by the antioxidant defense system of tumor cells, particularly reduced glutathione (GSH). To address these limitations, we have developed a programmed activatable PS, designated as LET‐19, specifically designed for acidity/GSH dual‐locked PDT of tumors. LET‐19 is constructed upon an iodinated cyanine structure, incorporating an oxazinane moiety and a 3,5‐bis(trifluoromethyl)benzenethiol group. One lock is the oxazinane moiety that is capable of responding to acidic tumor microenvironment (TME), another lock is the 3,5‐bis(trifluoromethyl)benzenethiol group that reacts to GSH. Notably, the fluorescence (FL), photoacoustic (PA), and photodynamic properties of LET‐19 are initially suppressed. The programmed activation of acidity/GSH dual‐locked PS is achieved by following steps: i) Once LET‐19 enters tumor tissues, it is activated by the acidic TME; ii) Subsequently, LET‐19 is taken up by tumor cells and further activated by GSH. Only in the occurrence of H + and GSH, whether in vitro or in vivo, both of the responsive units were sequentially recognized, thereby restoring FL/PA signals and the photodynamic capability of LET‐19. This mechanism allows LET‐19 to perform precise tumor identification by FL/PA dual‐modality imaging, as well as improve the efficacy and safety of PDT. Meanwhile, in vitro and in vivo results demonstrate that LET‐19 depletes GSH to inhibit the activity of glutathione peroxidase 4, disrupting redox homeostasis and thus amplifying the efficacy of PDT. This study provides a strategy to construct programmed activatable PSs for precision photodynamic theranostics of tumors.