Wan Guoyun, Chen Jiayu, Zhou Yingying, Dou Lina, Wang Dongmei, Wang Nannan, Chen Hongli, Wang Haijiao, Wang Xianwen, Yang Zhijun, Ding Dan
The Key Laboratory of Biomedical Material, School of Life Science and Technology, Xinxiang Medical University, Xinxiang, 453003, PR China.
School of Electrical Engineering and Automation, Henan Institute of Technology, Xinxiang, 453003, PR China.
Bioact Mater. 2025 Aug 2;53:718-736. doi: 10.1016/j.bioactmat.2025.07.032. eCollection 2025 Nov.
Monomodal therapies often fail to eradicate tumors due to the complexity of tumorigenesis and microenvironmental resistance. Electrodynamic therapy (EDT) and cuproptosis as emerging antitumor therapies have attracted widespread attention and become the promising strategies for tumor treatment due to their unique advantages. Here, we first time present a light-cured millineedle as a tool for co-delivering a nano-pomegranate (N-PG) platform and Cu by integrating EDT and cuproptosis induction for combined oral cancer treatment. This platform N-PG/NSC consists of Pt-doped dendritic mesoporous large silica nanoparticles (Pt@DLMSN) loaded copper ionophore NSC319726, enabling dual therapeutic actions: (1) N-PG/NSC-based EDT-driven generation of hydroxyl radicals (•OH) via HO decomposition under electric fields, circumventing hypoxia-related resistance, and (2) NSC imported Cu-mediated cuproptosis through mitochondrial dysfunction induced by DLAT oligomerization and Fe-S cluster protein depletion. The millineedle ensures precise and weak-leakage intratumoral delivery, while simultaneously triggering immunogenic cell death (ICD) to prime antitumor immunity. When combined with the TLR7/8 agonist R848, the platform elicits systemic immune activation, effectively suppressing both primary and abscopal oral tumors. As the first reported integration of MN-assisted drug delivery, hypoxia-tolerant EDT, and cuproptosis, this work establishes a translatable paradigm for multimodal cancer therapy, merging localized cytotoxicity with immune reprogramming for enhanced clinical outcomes.
由于肿瘤发生的复杂性和微环境抗性，单峰疗法往往无法根除肿瘤。电动力疗法（EDT）和铜死亡作为新兴的抗肿瘤疗法，因其独特优势而备受关注，成为肿瘤治疗的有前景策略。在此，我们首次展示一种光固化微针，作为一种将纳米石榴（N-PG）平台和铜共同递送的工具，通过整合EDT和诱导铜死亡来联合治疗口腔癌。该N-PG/NSC平台由负载铜离子载体NSC319726的铂掺杂树枝状介孔大二氧化硅纳米颗粒（Pt@DLMSN）组成，具有双重治疗作用：（1）基于N-PG/NSC的EDT在电场作用下通过水分解驱动产生羟基自由基（•OH），规避缺氧相关抗性；（2）NSC导入的铜通过DLAT寡聚化和铁硫簇蛋白消耗诱导的线粒体功能障碍介导铜死亡。微针确保肿瘤内精确且低泄漏的递送，同时触发免疫原性细胞死亡（ICD）以启动抗肿瘤免疫。当与TLR7/8激动剂R848联合使用时，该平台引发全身免疫激活，有效抑制原发性和远隔口腔肿瘤。作为首次报道的微针辅助药物递送、耐缺氧EDT和铜死亡的整合，这项工作建立了一种可转化的多模态癌症治疗范式，将局部细胞毒性与免疫重编程相结合以提高临床疗效。
