Wang Chaoyu, Liu Huiming, Liu Shuai, Wang Zhijun, Zhang Jianhua
School of Chemistry and Chemical Engineering, Mudanjiang Normal University, Mudanjiang, China.
Key Laboratory of Systems Bioengineering of the Ministry of Education, Department of Polymer Science and Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.
Front Chem. 2020 Jun 26;8:488. doi: 10.3389/fchem.2020.00488. eCollection 2020.
Cancer poses a serious threat to human health. To enhance the efficacy of tumor chemotherapy, it is urgent to develop novel and effective nanocarriers with the ability to efficiently load and deliver anticancer drugs. Covalent organic frameworks (COF)-based nanocarriers (CONs) have exhibited great potential for drug loading due to their porous structure and high surface area. However, the function of tumor intracellular-triggered drug release has barely been integrated. Herein we first synthesized a kind of hydrazide and disulfide bonds containing building block (4,4'-Dihydrazide diphenyl disulfide, ), which was used to develop a PEGylated pH and redox dual-sensitive CONs (denoted HY/SS-CONs) for efficiently loading and delivering doxorubicin (DOX). The obtained HY/SS-CONs can achieve a very high loading content of DOX and very low premature leakage at physiological condition. However, under tumor intracellular microenvironment, HY/SS-CONs with acid-cleavable hydrazone bonds, and GSH-exchangeable disulfide bonds will undergo rapid disintegration, and efficiently release DOX to kill tumor cells. The COFs-based dual-sensitive nanocarriers provide a promising solution to the dilemma of extracellular drug loading and tumor intracellular drug release.
癌症对人类健康构成严重威胁。为提高肿瘤化疗疗效，迫切需要开发具有高效负载和递送抗癌药物能力的新型有效纳米载体。基于共价有机框架（COF）的纳米载体（CONs）因其多孔结构和高比表面积而在药物负载方面展现出巨大潜力。然而，肿瘤细胞内触发药物释放的功能几乎未被整合。在此，我们首先合成了一种含酰肼和二硫键的结构单元（4,4'-二酰肼二苯基二硫化物），用于开发一种聚乙二醇化的pH和氧化还原双敏感CONs（记为HY/SS-CONs），以高效负载和递送阿霉素（DOX）。所得到的HY/SS-CONs在生理条件下能实现非常高的DOX负载量和非常低的过早泄漏。然而，在肿瘤细胞内微环境中，具有酸可裂解腙键和谷胱甘肽可交换二硫键的HY/SS-CONs会迅速分解，并有效释放DOX以杀死肿瘤细胞。基于COFs的双敏感纳米载体为细胞外药物负载和肿瘤细胞内药物释放的困境提供了一种有前景的解决方案。
