A Glycosylated Covalent Organic Framework Equipped with BODIPY and CaCO 3 for Synergistic Tumor Therapy

Abstract Ca 2+ , a ubiquitous but nuanced modulator of cellular physiology, is meticulously controlled intracellularly. However, intracellular Ca 2+ regulation, such as mitochondrial Ca 2+ buffering capacity, can be disrupted by 1 O 2 . Thus, the intracellular Ca 2+ overload, which is recognized as one of the important cell pro‐death factors, can be logically achieved by the synergism of 1 O 2 with exogenous Ca 2+ delivery. Reported herein is a nanoscale covalent organic framework (NCOF)‐based nanoagent, namely CaCO 3 @COF‐BODIPY‐2I@GAG ( 4 ), which is embedded with CaCO 3 nanoparticle (NP) and surface‐decorated with BODIPY‐2I as photosensitizer (PS) and glycosaminoglycan (GAG) targeting agent for CD44 receptors on digestive tract tumor cells. Under illumination, the light‐triggered 1 O 2 not only kills the tumor cells directly, but also leads to their mitochondrial dysfunction and Ca 2+ overload. An enhanced antitumor efficiency is achieved via photodynamic therapy (PDT) and Ca 2+ overload synergistic therapy.