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

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 1O2. Thus, the intracellular Ca2+ overload, which is recognized as one of the import...

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Published inAngewandte Chemie International Edition Vol. 59; no. 41; pp. 18042 - 18047
Main Authors Guan, Qun, Zhou, Le‐Le, Lv, Fan‐Hong, Li, Wen‐Yan, Li, Yan‐An, Dong, Yu‐Bin
Format Journal Article
LanguageEnglish
Published Weinheim Wiley Subscription Services, Inc 05.10.2020
EditionInternational ed. in English
Subjects
Calcium (intracellular)
Calcium (mitochondrial)
Calcium buffering
Calcium carbonate
Calcium ions
calcium overload
cancer
Cancer therapies
CD44 antigen
Cell death
covalent organic frameworks
Gastrointestinal tract
Glycosaminoglycans
Intracellular
Mitochondria
Nanoparticles
Overloading
Photodynamic therapy
reticular chemistry
Synergism
Tumor cells
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Summary: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 1O2. 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 1O2 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 1O2 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. A multifunctional COF‐based nanoagent, which is equipped with BODIPY‐2I photosensitizer, CaCO3 nanoparticle, and glycosaminoglycan (GAG) targeting agent, can be a highly efficient and selective antitumor nanomedicine for colon tumor via photodynamic therapy (PDT) and Ca2+ overload synergistic therapy.
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ISSN:1433-7851
1521-3773
1521-3773
DOI:10.1002/anie.202008055