H2O2 Self‐Supplied Chemodynamic Nanosystem Enhanced by Ca2+ Interference and Starvation Strategy for Targeted Cancer Therapy

IF 2.7 4区 材料科学 Q3 CHEMISTRY, PHYSICAL
Lei Shi, Yao‐Jia Ma, Xing‐Hui Ren, Zheng‐Chen Su, Xi‐Wen He, Wen‐You Li, Yu‐Kui Zhang
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引用次数: 0

Abstract

Chemodynamic therapy (CDT) has received increasing attention in recent years due to its effectiveness and specificity. However, the limited endogenous hydrogen peroxide (H2O2) concentration and resistance to reactive oxygen species in cancer cells hinder the further application of CDT. Here, an H2O2 self‐supplied nanosystem FCaO2@ZIF‐67‐2‐DG‐FA (FZDF) is synthesized to achieve efficient CDT improvement by Ca2+ overload and starvation therapy. Under folic acid‐mediated tumor targeting and endocytosis, the ZIF‐67 layer of FZDF is cleaved in the mildly acidic environment, releasing Co2+ and 2‐deoxy‐D‐glucose (2‐DG). The decomposition of exposed FCaO2 generates sufficient H2O2, which further produces abundant OH via the Fenton‐like reaction of Co2+. Simultaneously, Ca2+ overload‐triggered mitochondrial dysfunction couples with glycolysis inhibition via 2‐DG‐induced starvation, which disrupts intracellular adenosine triphosphate (ATP) synthesis and amplifies the efficacy of CDT. Silicon nanoparticles released from FCaO2 are applied as in vitro fluorescent probes to image tumor cells overexpressing folate receptors. The results have presented that FZDF can actively accumulate in tumor cells, causing the mitochondrial membrane potential abnormality and a decrease in intracellular ATP content, thereby enhancing the self‐supplied CDT with less effect on normal cells and tissues. This work provides a novel strategy for constructing effective CDT nanosystems by hindering intracellular energy supply.
通过 Ca2+ 干扰和饥饿策略增强的 H2O2 自供化学动力学纳米系统用于癌症靶向治疗
化学动力疗法(CDT)因其有效性和特异性近年来受到越来越多的关注。然而,内源性过氧化氢(H2O2)浓度有限以及癌细胞对活性氧的抗性阻碍了化学动力疗法的进一步应用。本文合成了一种自供H2O2的纳米系统FCaO2@ZIF-67-2-DG-FA(FZDF),通过Ca2+过载和饥饿疗法实现高效的CDT改善。在叶酸介导的肿瘤靶向和内吞作用下,FZDF的ZIF-67层在弱酸性环境中被裂解,释放出Co2+和2-脱氧-D-葡萄糖(2-DG)。暴露在外的 FCaO2 分解产生充足的 H2O2,通过 Co2+ 的 Fenton 类反应进一步产生大量 -OH。与此同时,Ca2+ 过载引发的线粒体功能障碍与 2-DG 诱导的饥饿抑制糖酵解相结合,破坏了细胞内三磷酸腺苷(ATP)的合成,扩大了 CDT 的功效。从 FCaO2 中释放出的硅纳米粒子被用作体外荧光探针,对过度表达叶酸受体的肿瘤细胞进行成像。研究结果表明,FZDF能在肿瘤细胞中主动积聚,导致线粒体膜电位异常和细胞内ATP含量下降,从而增强自供CDT,对正常细胞和组织的影响较小。这项工作为通过阻碍细胞内能量供应来构建有效的 CDT 纳米系统提供了一种新策略。
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来源期刊
Particle & Particle Systems Characterization
Particle & Particle Systems Characterization 工程技术-材料科学:表征与测试
CiteScore
5.50
自引率
0.00%
发文量
114
审稿时长
3.0 months
期刊介绍: Particle & Particle Systems Characterization is an international, peer-reviewed, interdisciplinary journal focusing on all aspects of particle research. The journal joined the Advanced Materials family of journals in 2013. Particle has an impact factor of 4.194 (2018 Journal Impact Factor, Journal Citation Reports (Clarivate Analytics, 2019)). Topics covered include the synthesis, characterization, and application of particles in a variety of systems and devices. Particle covers nanotubes, fullerenes, micelles and alloy clusters, organic and inorganic materials, polymers, quantum dots, 2D materials, proteins, and other molecular biological systems. Particle Systems include those in biomedicine, catalysis, energy-storage materials, environmental science, micro/nano-electromechanical systems, micro/nano-fluidics, molecular electronics, photonics, sensing, and others. Characterization methods include microscopy, spectroscopy, electrochemical, diffraction, magnetic, and scattering techniques.
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