College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.
Anal Chem. 2021 Aug 31;93(34):11751-11757. doi: 10.1021/acs.analchem.1c02105. Epub 2021 Aug 16.
Developing nanoplatforms that simultaneously integrate diagnostic imaging and therapy functions has been a promising but challenging task for cancer theranostics. Herein, we report the rational design of a smart nucleic acid-gated covalent organic framework (COF) nanosystem for cancer-specific imaging and microenvironment-responsive drug release. Cy5 dye-labeled single-stranded DNA (ssDNA) for mRNA recognition was adsorbed on the surface of doxorubicin (Dox)-loaded COF nanoparticles (NPs). Dox loaded in the pores of COF NPs could strengthen the interactions between ssDNA and COF and enhance the fluorescence quenching effect toward Cy5, while the densely coated ssDNA could prevent the leakage of Dox from COF NPs. The obtained nanosystem exhibited low fluorescence signal and Dox release in normal cells; however, the ssDNA could be released by the overexpressed TK1 mRNA in cancer cells to recover the intense fluorescence signal of Cy5, and the loaded Dox could be further released for chemotherapy. Therefore, cancer cell-specific diagnostic imaging and drug release were realized with the rationally developed nanosystem. This work offers a universal nanoplatform for cancer theranostics and a promising strategy for regulating the interaction between COFs and biomolecules.
开发同时集成诊断成像和治疗功能的纳米平台一直是癌症治疗学的一项有前途但具有挑战性的任务。在此，我们报告了一种智能核酸门控共价有机框架（COF）纳米系统的合理设计，用于癌症特异性成像和微环境响应性药物释放。用于 mRNA 识别的 Cy5 染料标记的单链 DNA（ssDNA）被吸附在载有阿霉素（DOX）的 COF 纳米颗粒（NPs）的表面上。DOX 负载在 COF NPs 的孔中可以增强 ssDNA 和 COF 之间的相互作用，并增强对 Cy5 的荧光猝灭效应，而密集包覆的 ssDNA 可以防止 DOX 从 COF NPs 中泄漏。所得到的纳米系统在正常细胞中表现出低荧光信号和 DOX 释放；然而，ssDNA 可以被癌细胞中过表达的 TK1 mRNA 释放，以恢复 Cy5 的强烈荧光信号，并且负载的 DOX 可以进一步释放用于化学治疗。因此，通过合理开发的纳米系统实现了癌细胞特异性诊断成像和药物释放。这项工作为癌症治疗学提供了一种通用的纳米平台，并为调节 COF 与生物分子之间的相互作用提供了一种有前途的策略。
