A Glycosylated Covalent Organic Framework Equipped with BODIPY and CaCO3for Synergistic Tumor Therapy

Ca2+, 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 CaCO3@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.