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

Abstract

Ca²⁺ , a ubiquitous but nuanced modulator of cellular physiology, is meticulously controlled intracellularly. However, intracellular Ca²⁺ regulation, such as mitochondrial Ca²⁺ buffering capacity, can be disrupted by ¹ O₂ . Thus, the intracellular Ca²⁺ overload, which is recognized as one of the important cell pro-death factors, can be logically achieved by the synergism of ¹ O₂ with exogenous Ca²⁺ delivery. Reported herein is a nanoscale covalent organic framework (NCOF)-based nanoagent, namely CaCO₃ @COF-BODIPY-2I@GAG (4), which is embedded with CaCO₃ 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 O₂ not only kills the tumor cells directly, but also leads to their mitochondrial dysfunction and Ca²⁺ overload. An enhanced antitumor efficiency is achieved via photodynamic therapy (PDT) and Ca²⁺ overload synergistic therapy.

Keywords: calcium overload; cancer; covalent organic frameworks; photodynamic therapy; reticular chemistry.