DNAzyme-based gene therapy faces some challenges including cell penetration, activity limitation, and co-delivery functions. Self-assembled DNA nanomedicine has attracted widespread attention due to its many advantages. It is urgent to develop a universal DNA degradation strategy for precise programmable drug release. Herein, we reported a self-catabolic DNAzyme nanospheres (SCNS), which could simultaneously achieve cell penetration, activity enhancement, and co-delivery functions. The SCNS were assembled through Y-DNA stepwise hybridization with each other, which were then loaded with aptamer (Apt), doxorubicin (Dox), and zinc oxide nanoparticles (ZnO NPs). The acid-triggered dissociation of ZnO NPs leads to the generation of Zn²⁺ ions cofactors for immediately self-catabolic DNAzyme nanospheres. After the disassembly of the SCNS, three types of anticancer treatments would be activated, which include Zn²⁺ involved reactive oxygen species (ROS), Dox-induced chemotherapy, and DNAzyme-based gene therapy. The experimental results show that the nanoplatform (Apt-SCNS-Dox-ZnO) has a good tumor-killing effect and minimal side effects. As a smart self-driven drug delivery nanoplatform, it is anticipated to displace extraordinary potential in biomedicine and bioengineering.

基于 DNAzyme 的基因治疗面临一些挑战，包括细胞渗透、活性限制和共传递功能。自组装DNA纳米医学因其诸多优点而受到广泛关注。迫切需要开发一种通用的 DNA 降解策略来实现精确的可编程药物释放。在此，我们报道了一种自分解代谢DNAzyme纳米球（SCNS），它可以同时实现细胞渗透、活性增强和共递送功能。 SCNS 通过 Y-DNA 逐步杂交组装，然后装载适体 (Apt)、阿霉素 (Dox) 和氧化锌纳米颗粒 (ZnO NP)。 ZnO NP 的酸触发解离导致生成 Zn ²⁺ 离子辅助因子，用于立即自我分解代谢的 DNAzyme 纳米球。 SCNS解体后，三种类型的抗癌治疗将被激活，包括Zn ²⁺ 涉及活性氧（ROS）、Dox诱导的化疗和基于DNAzyme的基因治疗。实验结果表明，纳米平台（Apt-SCNS-Dox-ZnO）具有良好的杀瘤效果和最小的副作用。作为一种智能自驱动药物输送纳米平台，它有望在生物医学和生物工程领域发挥巨大的潜力。