A Glycosylated Covalent Organic Framework Equipped with BODIPY and CaCO3 for Synergistic Tumor Therapy.

Calcium (Ca 2+ ), as a ubiquitous but nuanced modulator of cellular physiology, its level is meticulously controlled intracellularly. However, the intracellular Ca 2+ regulation, such as mitochondrial Ca 2+ buffering capacity, can be readily 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 the digestive tract tumor cells. Under illumination, the light-triggered 1 O 2 can not only kill the tumor cells directly, but also lead to their mitochondrial dysfunction and Ca 2+ overload. As a result, a markedly enhanced antitumor efficiency is achieved via photodynamic therapy (PDT) and Ca 2+ overload synergistic therapy.