Yang Zeping, Qin Renpan, Ruan Deqiang, Hu Chong, Li Wenjing, Zhou Jie, Zhang Fan, Guo Bin, Huang Liyu, Jaque Daniel, Shen Yingli, Wang Fu
Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710126, China.
Institute of Medical Engineering, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
ACS Nano. 2025 Aug 5;19(30):27873-27889. doi: 10.1021/acsnano.5c09287. Epub 2025 Jul 26.
Breast cancer remains a leading cause of mortality among women globally, underscoring the critical need for effective theranostic strategies. MicroRNA-21 (miR-21) imaging-guided photodynamic therapy (PDT) has attracted significant attention in recent years due to its selectivity and sensitivity toward breast cancer. However, key challenges remain, particularly regarding the low abundance of miR-21 caused by low-quality imaging at the tumor site and the low efficiency of PDT. To address these issues, we developed theranostic Ce6-DNAzyme@ZIF-8@PEG nanoparticles (CDZP NPs) for breast cancer, which integrates dual-cycling signal amplification for miR-21 detection and enhanced PDT through GPX4-DNAzyme-mediated gene editing to inhibit reactive oxygen species (ROS) scavenging. The CDZP NPs are based on a dodecahedral metal-organic framework (MOF) ZIF-8, encapsulating a dual-cycling miR-21 imaging system and Ce6-DNAzyme therapeutic system one-pot synthesis. CDZP NPs exhibit excellent biocompatibility, acid-responsive release behavior, and a high loading capacity. These properties enable the control release of Zn, Ce6, and dual-cycling signal magnification system for miR-21 detection and enhanced PDT. studies with tumor-bearing mice demonstrated that intravenous injection of CDZP NPs could effectively target tumors. The dual-cycling signal amplification system, comprising three hairpin probes (H, H, and H), achieved a detection limit for miR-21 as low as 3.4 pM. Moreover, Zn-activated GPX4-DNAzyme significantly inhibited GPX4 protein expression, reducing ROS scavenging and further enhancing PDT efficiency with a high tumor inhibition rate of 72.3%. This proposed theranostic strategy holds promise for advancing precision theranostics in breast cancer treatment.
乳腺癌仍然是全球女性死亡的主要原因，这凸显了对有效诊疗策略的迫切需求。近年来，微小RNA-21（miR-21）成像引导的光动力疗法（PDT）因其对乳腺癌的选择性和敏感性而备受关注。然而，关键挑战依然存在，特别是肿瘤部位成像质量低导致miR-21丰度低以及PDT效率低的问题。为了解决这些问题，我们开发了用于乳腺癌的诊疗一体化Ce6-脱氧核酶@ZIF-8@PEG纳米颗粒（CDZP NPs），它集成了用于miR-21检测的双循环信号放大，并通过GPX4-脱氧核酶介导的基因编辑增强PDT以抑制活性氧（ROS）清除。CDZP NPs基于十二面体金属有机框架（MOF）ZIF-8，通过一锅法合成封装了双循环miR-21成像系统和Ce6-脱氧核酶治疗系统。CDZP NPs表现出优异的生物相容性、酸响应释放行为和高负载能力。这些特性能够实现锌、Ce6的控释以及用于miR-21检测和增强PDT的双循环信号放大系统。对荷瘤小鼠的研究表明，静脉注射CDZP NPs能够有效靶向肿瘤。由三个发夹探针（H1、H2和H3）组成的双循环信号放大系统实现了低至3.4 pM的miR-21检测限。此外，锌激活的GPX4-脱氧核酶显著抑制GPX4蛋白表达，减少ROS清除，并以72.3%的高肿瘤抑制率进一步提高PDT效率。这种提出的诊疗策略有望推动乳腺癌治疗中的精准诊疗。
