Staggered Stacking Covalent Organic Frameworks for Boosting Cancer Immunotherapy,Advanced Functional Materials

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Staggered Stacking Covalent Organic Frameworks for Boosting Cancer Immunotherapy
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2022-04-27 , DOI: 10.1002/adfm.202201542
Liang Zhang _{1,

2} , Yao Xiao ₁ , Qi‐Chao Yang ₁ , Lei‐Lei Yang ₁ , Shu‐Cheng Wan ₁ , Shuo Wang ₁ , Lu Zhang ₁ , Hexiang Deng ₂ , Zhi‐Jun Sun ₁

Affiliation

The synergistic efficacy of phototherapy and cancer immunotherapy is severely restricted by both the inherent photobleaching and aggregation-caused quench (ACQ) defects of photosensitizers and the intrinsic antioxidant tumor microenvironment (TME), such as hypoxia and overexpressed glutathione (GSH). To address these issues, a novel porphyrin-based staggered stacking covalent organic framework (COF), COF-618-Cu, is rationally designed as a reactive oxygen species (ROS) amplifier, owing to its excellent catalase-like activity, COF-618-Cu is capable of consuming endogenous hydrogen peroxide to produce sufficient oxygen to alleviate the tumor hypoxia phenomena. Moreover the overexpressed intracellular GSH is also depleted to decrease the scavenging of ROS, due to the glutathione peroxidase mimic activity of COF-618-Cu. Mechanistic studies reveal that the unique staggered stacking mode between COF-618-Cu interlayers can effectively relieve both the photobleaching and ACQ effects that are inaccessible to commonly eclipsed COFs. These, combined with their excellent photothermal therapy performance, make COF-618-Cu favorable for inducing robust immunogenic cell death and remodeling TME to boost antitumor immunity.

中文翻译：

用于促进癌症免疫疗法的交错堆叠共价有机框架

光疗法和癌症免疫疗法的协同功效受到光敏剂固有的光漂白和聚集引起的猝灭 (ACQ) 缺陷以及内在抗氧化肿瘤微环境 (TME) 的严重限制，例如缺氧和过表达的谷胱甘肽 (GSH)。为了解决这些问题，一种新颖的基于卟啉的交错堆叠共价有机框架（COF）COF-618-Cu，由于其优异的过氧化氢酶活性COF-618，被合理地设计为活性氧（ROS）放大器。 -Cu能够消耗内源性过氧化氢产生足够的氧气来缓解肿瘤缺氧现象。此外，由于 COF-618-Cu 的谷胱甘肽过氧化物酶模拟活性，过表达的细胞内 GSH 也被耗尽以减少 ROS 的清除。机理研究表明，COF-618-Cu 中间层之间独特的交错堆叠模式可以有效地缓解通常黯然失色的 COF 无法获得的光漂白和 ACQ 效应。这些，再加上其出色的光热治疗性能，使 COF-618-Cu 有利于诱导强大的免疫原性细胞死亡和重塑 TME 以增强抗肿瘤免疫力。

更新日期：2022-04-27

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