纳米共价有机框架（NCOF）作为新兴的药物递送纳米载体近年来在生物医学领域受到广泛关注。然而，关于pH响应性NCOFs在药物递送纳米系统中的应用的报道很少。在这项工作中，腙修饰的 NCOF 作为 pH 触发的分子开关，旨在用于有效的癌症治疗。这些在通道壁上带有腙基团的功能化 NCOF（称为 NCOF-NHNH2）是通过合成后修饰策略获得的。随后，通过共价连接负载抗癌药物阿霉素（DOX）作为模型分子，产生NCOFs-NN-DOX。最后，将大豆磷脂（SP）包覆在HNTs-NN-DOX表面，命名为NCOFs-NN-DOX@SP，进一步增强HNTs在生理溶液中的分散性、稳定性和生物相容性。 NCOFs-NN-DOX@SP 显示出优异且智能的缓释效果，在 pH = 5.2 时比在 pH = 7.4 时增加了近六倍。 NCOFs-NN-DOX@SP 的体外细胞毒性和成像测定对 Lewis 肺癌（LLC）细胞表现出增强的治疗效果，表明所制备的 NCOFs 在癌症治疗中具有巨大的潜力。因此，这项工作为设计刺激响应性功能化 NCOF 提供了一种新方法，并促进了它们作为按需药物输送系统在癌症治疗领域的潜在应用。该期刊版权所有 © 英国皇家化学学会。

Nanoscale covalent organic frameworks (NCOFs) as emerging drug-delivery nanocarriers have received much attention in biomedicine in recent years. However, there are few reports on the application of pH-responsive NCOFs for drug delivery nanosystems. In this work, hydrazone-decorated NCOFs as pH-triggered molecular switches are designed for efficient cancer therapy. These functionalized NCOFs with hydrazone groups on the channel walls (named NCOFs-NHNH2) are obtained via a post-synthetic modification strategy. Subsequently, the anticancer drug doxorubicin (DOX) as the model molecule is loaded through covalent linkage to yield NCOFs-NN-DOX. Finally, soybean phospholipid (SP) is coated on the surface of HNTs-NN-DOX, named NCOFs-NN-DOX@SP, to further enhance the dispersibility, stability and biocompatibility of HNTs in physiological solution. NCOFs-NN-DOX@SP showed an excellent and intelligent sustained-release effect with an almost sixfold increase at pH = 5.2 than at pH = 7.4. In vitro cell toxicity and imaging assays of NCOFs-NN-DOX@SP exhibited an enhanced therapeutic effect on Lewis lung carcinoma (LLC) cells, demonstrating that the fabricated NCOFs have a great potential in cancer therapy. Thus, this work provides a new way toward designing stimulus-responsive functionalized NCOFs and promotes their potential application as an on-demand drug delivery system in the field of cancer treatment.This journal is © The Royal Society of Chemistry.