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

Ca , a ubiquitous but nuanced modulator of cellular physiology, is meticulously controlled intracellularly. However, intracellular Ca regulation, such as mitochondrial Ca buffering capacity, can be disrupted by O . Thus, the intracellular Ca overload, which is recognized as one of the important cell pro-death factors, can be logically achieved by the synergism of O with exogenous Ca delivery. Reported herein is a nanoscale covalent organic framework (NCOF)-based nanoagent, namely CaCO @COF-BODIPY-2I@GAG (4), which is embedded with CaCO 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 O not only kills the tumor cells directly, but also leads to their mitochondrial dysfunction and Ca overload. An enhanced antitumor efficiency is achieved via photodynamic therapy (PDT) and Ca overload synergistic therapy.