Design, synthesis, and biological evaluation of BODIPY-based photoactivatable Crizotinib prodrugs for precision cancer therapy.

Crizotinib is an established first-line therapy for patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC). However, long-term treatment is often associated with systemic toxicity, leading to various adverse effects that compromise patient outcomes. Herein, we report the design of novel BODIPY-based photoactivatable Crizotinib prodrugs to achieve precise spatiotemporal control over drug activity. The boron-dipyrromethene (BODIPY) chromophore was selected as the photolabile protecting group due to its excellent photophysical properties, including tunable absorption within the tissue-penetrating near-infrared (NIR) window, high photostability, and synthetic versatility, offering significant advantages over conventional UV-cleavable groups. Upon light irradiation, the caged compound undergoes efficient uncaging to release active Crizotinib, restoring its potent kinase inhibitory and antiproliferative activities. This work establishes BODIPY-caged Crizotinib as a promising photoactivatable agent for precision cancer therapy.