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可生物降解的共价有机框架实现肿瘤微环境响应药物释放和抗肿瘤治疗。

Biodegradable covalent organic frameworks achieving tumor micro-environment responsive drug release and antitumor treatment.

机构信息

Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.

School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China.

出版信息

Biomater Sci. 2023 Sep 26;11(19):6524-6536. doi: 10.1039/d3bm01088k.

Abstract

The emergence of nanocarriers has greatly improved the therapeutic efficacy of chemotherapeutic drugs. As emerging nanocarriers, covalent organic frameworks (COFs) have been increasingly used in biomedicine in recent years. However, due to their inherent chemical stability, existing COF nanocarriers hardly undergo degradation, which brings potential safety hazards to further applications. In this work, we introduce the azo bond into COFs. When the nanocarrier enters the cell, ˙OH generated by the coordinated Fe response to the HO in the cell will break the azo bond and cause the degradation of the framework structure, accelerating the release of internally loaded DOX to effectively realize tumor treatment. We verified the degradation ability of the materials by constructing model compounds, drug release, MTT assay and antitumor experiments. Compared with the control groups, the degradable COF accelerates the release of DOX and shows a stronger killing effect on 4T1 cells. Serum biochemical analysis and H&E sections of organs show good biocompatibility for both COFs and degradation products. This work provides a new idea for the design of biodegradable COFs , and greatly explores the potential application of COF materials in the biomedical field.

摘要

纳米载体的出现极大地提高了化疗药物的治疗效果。作为新兴的纳米载体,共价有机框架(COFs)近年来在生物医学领域中的应用越来越广泛。然而,由于其内在的化学稳定性,现有的 COF 纳米载体几乎不会发生降解,这给进一步的应用带来了潜在的安全隐患。在这项工作中,我们将偶氮键引入 COFs 中。当纳米载体进入细胞时,由配位 Fe 产生的˙OH 响应细胞中的 HO 将打破偶氮键并导致框架结构的降解,加速内部装载的 DOX 的释放,从而有效地实现肿瘤治疗。我们通过构建模型化合物、药物释放、MTT 测定和抗肿瘤实验验证了材料的降解能力。与对照组相比,可降解 COF 加速了 DOX 的释放,并对 4T1 细胞表现出更强的杀伤作用。血清生化分析和器官的 H&E 切片显示 COFs 和降解产物均具有良好的生物相容性。这项工作为可生物降解 COFs 的设计提供了新的思路,并极大地探索了 COF 材料在生物医学领域的潜在应用。

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