Bio-Design and Manufacturing  2026 Vol.9 No.5 P.825 - 844

http://doi.org/10.1631/bdm.2500656


Dual-targeting by rotating magnetic field-driven superparamagnetic bionic nanorobots for enhanced triple-negative breast cancer therapy


Author(s):  Wei Song,Zhongxin Liu,Jia Xu,Zhihong Wang,Guixing Zhou,Jianfeng Wang,Quan Zhou,Kaiting Zhao,Ayesha Younas,Shuanghu Wang,Yong Shi

Affiliation(s):  1. Department of Thoracic Surgery, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing 314000, China more

Corresponding email(s):   ay.ayeshayounas@gmail.com, wangshuanghu@lsu.edu.cn, shiyong111@163.com

Key Words:  Biomimetic membrane, Magnetic bionic nanorobots, Ferroptosis, Magnetic guidance, Triple-negative breast cancer


Wei Song, Zhongxin Liu, Jia Xu, Zhihong Wang, Guixing Zhou, Jianfeng Wang, Quan Zhou, Kaiting Zhao, Ayesha Younas, Shuanghu Wang, Yong Shi. Dual-targeting by rotating magnetic field-driven superparamagnetic bionic nanorobots for enhanced triple-negative breast cancer therapy[J]. Journal of Zhejiang University Science D, 2026, 9(5): 825 - 844.

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Abstract: 
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with limited treatment options and poor prognosis due to the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). Doxorubicin (DOX) -based chemotherapy remains the standard of care, yet dose-limiting cardiotoxicity and rapid chemoresistance compromise efficacy. To overcome these hurdles, we engineered rotating magnetic field-driven nanorobots (MFDNs) comprising DOX-loaded hollow mesoporous iron oxide nanoparticles cloaked with 4T1 cancer cell membranes. Under a rotating magnetic field (RMF; 5 Hz, 100 mT), MFDNs self-assemble into dynamic chains, evading the aggregation that plagues static magnetic field approaches and enabling deep intratumoral penetration. This dual-targeting mechanism, passive homing via membrane recognition and active navigation via RMF, delivers a three-fold higher intracellular DOX concentration than uncoated carriers. Mechanistically, MFDNs depleted intracellular glutathione by 70%, suppressed glutathione peroxidase-4 (GPX4), and elevated Fe2+, reactive oxygen species (ROS), and lipid peroxidation, thereby triggering robust ferroptosis. In 4T1 tumor-bearing mice, intravenous MFDNs plus RMF shrank tumors by 90% compared with 45% for free DOX, without systemic toxicity or weight loss. Histopathology confirmed extensive necrosis, abundant ferroptosis markers, and negligible off-target accumulation. Collectively, the seamless integration of dynamic RMF guidance with biomimetic membrane cloaking positions MFDNs as a clinically translatable nanoplatform that overcomes chemoresistance and markedly improves therapeutic outcomes for TNBC.

旋转磁场驱动的超顺磁仿生纳米机器人双重靶向以增强三阴性乳腺癌治疗效果

三阴性乳腺癌(TNBC)是一种侵袭性极强的乳腺癌亚型,因缺乏雌激素受体、孕激素受体及人表皮生长因子受体 2(HER2)受体,治疗手段十分有限,预后较差。以阿霉素(DOX)为基础的化疗目前仍是标准治疗方案,但其剂量限制性心脏毒性和快速出现的化疗耐药性严重削弱了疗效。为应对这些挑战,我们设计了一种可由旋转磁场驱动的纳米机器人(MFDNs)。该纳米机器人以负载阿霉素的空心介孔氧化铁纳米粒子为核心,外层包裹 4T1 乳腺癌细胞膜。在旋转磁场(RMF;5 Hz,100 mT)作用下,MFDNs 能够自发组装成动态链状结构,避免了静态磁场(SMF)体系中常见的不可控聚集状态,从而具备深入肿瘤组织的能力。得益于“细胞膜介导的被动归巢”与“旋转磁场驱动的主动导航”的协同作用,MFDNs 使肿瘤细胞内的阿霉素浓度比未包膜载体提高了三倍。机制研究表明,MFDNs 可降低细胞内谷胱甘肽水平达 70%,抑制谷胱甘肽过氧化物酶 4(GPX4)活性,同时显著升高 Fe2+、活性氧(ROS)及脂质过氧化物水平,从而高效触发铁死亡。在 4T1 荷瘤小鼠模型中,静脉注射 MFDNs 并联合旋转磁场治疗,可使肿瘤体积缩小 90%,而相同剂量的游离 DOX 仅缩小 45%;同时,治疗组未出现全身毒性或体重减轻。组织病理学分析进一步证实,治疗组肿瘤组织呈大面积坏死,富集铁死亡相关标志物,且未见明显的脱靶蓄积。综上所述,动态旋转磁场引导与仿生细胞膜伪装的结合,使MFDNs 成为一种具备临床转化潜力的纳米平台,能够有效克服化疗耐药,显著改善三阴性乳腺癌的治疗效果。
关键词:仿生膜;磁性仿生纳米机器人;铁死亡;磁场引导;三阴性乳腺癌

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On-line Access: 2026-09-17

Received: 2025-12-23

Revision Accepted: 2026-04-22

Crosschecked: 0000-00-00

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Citations:  Bibtex RefMan EndNote GB/T7714

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