A Glycosylated Covalent Organic Framework Equipped with BODIPY and CaCO3for Synergistic Tumor Therapy
A Glycosylated Covalent Organic Framework Equipped with BODIPY and CaCO3for Synergistic Tumor Therapy
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DOI：
10.1002/anie.202008055
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发表时间：
2020-08-17
影响因子：
16.6
通讯作者：
Dong, Yu-Bin
中科院分区：
文献类型：
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作者：
Guan, Qun;Zhou, Le-Le;Dong, Yu-Bin
Ca 2+是一种普遍存在但微妙的细胞生理调节剂，在细胞内受到精心控制。然而，细胞内Ca（2+）调节，如线粒体Ca（2+）缓冲能力，可以被破坏（1）O（2）。因此，被认为是重要的细胞促死亡因子之一的细胞内Ca（2+）过载可以通过（1）O（2）与外源性Ca（2+）递送的协同作用而逻辑地实现。本文报道了一种基于纳米级共价有机框架（NCOF）的纳米剂，即CaCO 3 @COF-BODIPY-2I@GAG（4），其包埋有CaCO（3）纳米颗粒（NP）并表面修饰有BODIPY-2 I作为光敏剂（PS）和消化道肿瘤细胞上的CD 44受体的糖胺聚糖（GAG）靶向剂。光照条件下，光引发的（1）O（2）不仅直接杀伤肿瘤细胞，而且导致肿瘤细胞线粒体功能障碍和Ca（2+）超载。通过光动力疗法（PDT）和Ca（2+）过载协同疗法实现增强的抗肿瘤效率。
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.