Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 2, 2025

We report a tumor microenvironment-responsive photosensitizer (1) as molecular chameleon with cascade transformation capabilities for precision-controlled delivery. 1 is encapsulated in pH-responsive surfactant to form 1a PEGylated surface that does not generate ROS normal tissues. The generation activated by the overexpressed glutathione at acidic site yield 2 through an aromatic nucleophilic substitution. This of hydrophobic hydrophilic leads release size reduction, potentially enhancing drug accumulation and facilitating penetration. Furthermore, after treatment, deactivated γ-glutamyl transferase specific hydrolysis intramolecular rearrangement reactions, thereby reducing potential undesired phototoxicity. In vitro vivo studies show affords excellent phototoxicity cancer cells pyroptosis pathway. work offers promising strategy design chameleons control spatiotemporal delivery photosensitizes enhance photodynamic therapy efficacy.

Язык: Английский