Bio-Design and Manufacturing  2026 Vol.9 No.5 P.845 - 867

http://doi.org/10.1631/bdm.2600068


Stimuli-responsive magnetic black phosphorus-based nanoreactor for chirality-dependent anoikis induction in cancer therapy


Author(s):  Yan Wang,Jin Wu,Shicheng Li,Rencai Fan,Mingjun Li,Xin Liu,Cheng-song Yuan,Yuanyuan Chang,Zequn Ma,Chunxian Guo,Chang Ming Li,Bo Chen

Affiliation(s):  1. Institute of Materials Science and Devices, School of Materials Science and Engineering, Suzhou University of Science and Technology, Suzhou 215009, China more

Corresponding email(s):   ecmli@usts.edu.cn, chenbo@usts.edu.cn

Key Words:  Reactive oxygen species (ROS)-sensitive, Magnetic-laser stimuli-responsive, Chirality-dependent, Anoikis, Cancer therapy


Yan Wang, Jin Wu, Shicheng Li, Rencai Fan, Mingjun Li, Xin Liu, Cheng-song Yuan, Yuanyuan Chang, Zequn Ma, Chunxian Guo, Chang Ming Li, Bo Chen. Stimuli-responsive magnetic black phosphorus-based nanoreactor for chirality-dependent anoikis induction in cancer therapy[J]. Journal of Zhejiang University Science D, 2026, 9(5): 845 - 867.

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author="Yan Wang, Jin Wu, Shicheng Li, Rencai Fan, Mingjun Li, Xin Liu, Cheng-song Yuan, Yuanyuan Chang, Zequn Ma, Chunxian Guo, Chang Ming Li, Bo Chen",
journal="Journal of Zhejiang University Science D",
volume="9",
number="5",
pages="845 - 867",
year="2026",
publisher="Zhejiang University Press & Springer",
doi="10.1631/bdm.2600068"
}

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%A Yan Wang
%A Jin Wu
%A Shicheng Li
%A Rencai Fan
%A Mingjun Li
%A Xin Liu
%A Cheng-song Yuan
%A Yuanyuan Chang
%A Zequn Ma
%A Chunxian Guo
%A Chang Ming Li
%A Bo Chen
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%I Zhejiang University Press & Springer
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A1 - Yan Wang
A1 - Jin Wu
A1 - Shicheng Li
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A1 - Mingjun Li
A1 - Xin Liu
A1 - Cheng-song Yuan
A1 - Yuanyuan Chang
A1 - Zequn Ma
A1 - Chunxian Guo
A1 - Chang Ming Li
A1 - Bo Chen
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Abstract: 
Anoikis presents an alternative scheme for suppressing tumor metastasis. While limited by off-target effects, rapid degradation, and reactive oxygen species (ROS) accumulation, anoikis resistance remains a persistent challenge for current tumor therapy. The use of external and endogenous stimuli to trigger ROS bursts, as well as chirality-enhanced tumor microenvironment (TME) penetration, offers a valid solution. We developed a stimuli-responsive nanoreactor by coupling chiral histidine-modified manganese ferrite (MnFe2O4-PEG) nanoparticles with chiral cysteine-modified black phosphorus (BP) nanosheets via an ROS-sensitive thioketal (TK) bond to form a MnFe2O4-BP chiral magnetic nanoreactor (CT-MFBP). L-MFBP exhibited superior cellular uptake and intracellular retention due to its enhanced affinity for cell membranes. After entering the TME, the thioketal bond was cleaved by alternating magnetic field (AMF)-induced ROS, leading to the decomposition of the nanoreactor into chiral BP components. Subsequently, ROS accumulation was further amplified using BP-mediated photodynamic therapy (PDT). In addition, the nanoreactor demonstrated catalase (CAT)-like activity, converting endogenous H2O2 into O2, thereby effectively alleviating the tumor hypoxic microenvironment and enhancing PDT efficacy. Furthermore, these events activated the mitogen-activated protein kinase (MAPK)-caspase 3 signaling pathway by upregulating p38 protein and Bcl-2-modifying factor (BMF) expression, which together promoted anoikis in tumor cells—a finding further validated by genomic analysis. Both in vitro and in vivo results confirmed that L-MFBP provides a robust regulatory strategy to induce anoikis and suppress tumor metastasis, offering a promising approach for chiral magnetic nanomedicine in clinical antitumor applications.

刺激响应型磁性黑磷纳米反应器诱导手性依赖的肿瘤失巢凋亡的研究

失巢凋亡(anoikis)为抑制肿瘤转移提供了一种替代性策略。然而,当前基于失巢凋亡的肿瘤治疗仍受到脱靶效应、快速降解以及活性氧(ROS)积累不足等因素的限制,尤其面临失巢凋亡抵抗等关键难题。利用外源性和内源性刺激诱导 ROS 爆发,以及手性增强的肿瘤微环境(TME)穿透能力,为解决上述问题提供了一种有效的解决方案。本研究通过 ROS 响应性酮缩硫醇(TK)键,将手性组氨酸修饰的铁酸锰(MnFe2O4-PEG)纳米颗粒与手性半胱氨酸修饰的黑磷(BP)纳米片偶联,构建了一种刺激响应型 MnFe2O4-BP 手性磁性纳米反应器(CT-MFBP)。研究发现 L-MFBP 对肿瘤细胞膜具有更强的亲和性,相比 D 型材料获得更优异的细胞摄取能力和胞内滞留效率。进入肿瘤微环境后,在交变磁场(AMF)诱导产生的 ROS 作用下,TK 键发生断裂,促使纳米反应器解离并释放手性 BP。随后,通过 BP 介导的光动力治疗(PDT)进一步放大 ROS 积累效应。此外,该纳米反应器表现出类过氧化氢酶(CAT)活性,可将内源性 H2O2催化转化为 O2,从而有效缓解肿瘤缺氧微环境并增强 PDT 疗效。进一步研究表明,上述过程通过上调 p38 蛋白及 Bcl2 修饰因子(BMF)表达,激活 MAPK-caspase 3 信号通路,显著促进肿瘤细胞失巢凋亡,该机制亦得到了基因组学分析的验证。体内外实验结果均表明,L-MFBP 可作为一种高效调控策略,诱导失巢凋亡抑制肿瘤转移,为手性磁性纳米医学在肿瘤临床治疗中的应用提供了新的研究思路。
关键词:活性氧敏感;磁-光刺激响应;手性依赖;失巢凋亡;癌症治疗

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On-line Access: 2026-09-16

Received: 2026-01-29

Revision Accepted: 2026-05-09

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Citations:  Bibtex RefMan EndNote GB/T7714

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