(315) Self-Immolative Polymeric Prodrug for Targeted Cancer Therapy through Disturbing the Redox Balance

Introduction: Quinone methide (QM) depletes the antioxidant glutathione (GSH), increasing oxidative stress in cancer cells, making it a potential anticancer agent. However, its high reactivity with biomolecules leads to a short half-life and latent toxicity to normal cells. We developed a reactive oxygen species (ROS)-responsive self-immolative polymeric prodrug (SIPP) micelle that selectively releases QM in cancer cells and encapsulates 2-methoxy-β-estradiol (MBE), which increases intracellular ROS levels. Upon SIPP degradation, MBE is released, disturbing the redox balance and enhancing antitumor effects.