打破癌症治疗中的“打鼠”困境：超声波诱导的ROS风暴导致三模式细胞死亡
Breaking the "Whack-a-Mole" Dilemma in Cancer Therapy: Ultrasound-Propelled ROS Storm Enables Triple-Modal Cell Death.
摘要(中文译文)
纳米医学的进展使得精准诱导调节性细胞死亡（RCD）用于癌症治疗成为可能。尽管细胞凋亡仍是治疗的重要基石，但近年来铁死亡和铜死亡的发现开辟了新的治疗维度。然而，传统的铁死亡诱导剂存在稳定性差和易产生耐药性等局限性。纳米酶凭借其高催化活性和肿瘤微环境响应特性，为克服这些挑战提供了有前景的解决方案。为克服单一疗法常受限于代偿性通路和获得性耐药的局限，我们合理设计了一种声动力单原子铜纳米酶（CuSAE），实施“预耗竭与风暴放大”策略。该方法产生决定性的活性氧（ROS）风暴，作为主触发器同步激活三种不同的RCD通路：细胞凋亡、铁死亡和铜死亡，从而为对抗治疗耐药提供了创新性解决方案。在卵巢癌小鼠模型中，CuSAE展现出显著的杀瘤功效和稳健的治疗效果，确立其作为一种通过同时激活铁死亡和铜死亡来增强抗癌效果的多功能平台。
Abstract
Advances in nanomedicine have enabled precise induction of regulated cell death (RCD) for cancer therapy. While apoptosis remains a therapeutic cornerstone, the recent discovery of ferroptosis and cuproptosis has opened new therapeutic dimensions. However, conventional ferroptosis inducers suffer from limitations such as poor stability and susceptibility to drug resistance. Nanozymes, with their high catalytic activity and tumor microenvironment-responsive characteristics, offer promising solutions to these challenges. To overcome the limitations of monotherapies often constrained by compensatory pathways and acquired resistance, we rationally designed a sonodynamic single-atom copper nanozyme (CuSAE) that implements a "pre-depletion and storm amplification" strategy. This approach generates a decisive reactive oxygen species (ROS) storm that acts as a master trigger to synchronously activate three distinct RCD pathways: apoptosis, ferroptosis, and cuproptosis, thereby providing an innovative solution to combat therapeutic resistance. In mouse models of ovarian cancer, CuSAE demonstrated remarkable tumor-killing efficacy and robust therapeutic outcomes, establishing itself as a versatile platform that enhances anticancer effects through simultaneous activation of ferroptosis and cuproptosis.
如何引用
AMA
Menglin Luo, Lu Zhao, Min Zhang, Wen Fan, Wenjun Liu, Yu Yang, et al. Breaking the "Whack-a-Mole" Dilemma in Cancer Therapy: Ultrasound-Propelled ROS Storm Enables Triple-Modal Cell Death.. Small (Weinheim an der Bergstrasse, Germany). 2026; doi:10.1002/smll.202514512.
APA
Menglin Luo, Lu Zhao, Min Zhang, Wen Fan, Wenjun Liu, Yu Yang, et al (2026). Breaking the "Whack-a-Mole" Dilemma in Cancer Therapy: Ultrasound-Propelled ROS Storm Enables Triple-Modal Cell Death.. Small (Weinheim an der Bergstrasse, Germany). https://doi.org/10.1002/smll.202514512
GB/T 7714
Menglin Luo, Lu Zhao, Min Zhang, Wen Fan, Wenjun Liu, Yu Yang, et al. Breaking the "Whack-a-Mole" Dilemma in Cancer Therapy: Ultrasound-Propelled ROS Storm Enables Triple-Modal Cell Death.[J]. Small (Weinheim an der Bergstrasse, Germany), 2026 doi:10.1002/smll.202514512.
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