通过光热增强芬顿反应和谷胱甘肽抑制作用促进铁突变,实现肿瘤纳米催化协同治疗。

IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY
International Journal of Nanomedicine Pub Date : 2024-11-16 eCollection Date: 2024-01-01 DOI:10.2147/IJN.S480586
Qingcheng Song, Yiran Zhang, Hongzhi Hu, Xuemei Yang, Xin Xing, Jianhua Wu, Yanbin Zhu, Yingze Zhang
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引用次数: 0

摘要

导言:基于纳米技术的铁氧化驱动肿瘤消融策略可通过提高细胞内铁水平或抑制谷胱甘肽过氧化物酶 4 (GPX4) 的活性来实现。然而,细胞内的抗氧化防御机制赋予了肿瘤细胞抗铁蛋白沉积的能力。本研究的目的是开发一种协同治疗平台,以提高基于铁氧化作用的肿瘤疗法的疗效:方法:本研究开发了一种基于化学动力疗法(CDT)和光热疗法(PTT)的多功能纳米催化治疗平台(mFeB@PDA-FA),以有效触发肿瘤中的铁氧化酶。在我们的工作中,采用铁基介孔Fe3O4纳米颗粒(mFe3O4 NPs)包覆L-丁硫磺酰亚胺(BSO),然后在外围修饰叶酸功能化聚多巴胺(PDA)涂层。然后,利用人OS细胞(MNNG/HOS)和骨肉瘤皮下异种移植模型评估了mFeB@PDA-FA NPs的抗肿瘤效果。结果表明:含有多价元素(Fe2+/3+)的 mFe3O4 可将过氧化氢(H2O2)催化成具有高度细胞毒性的˙OH,而肿瘤微环境(TME)响应性释放的 BSO 分子可抑制 GSH 的生物合成,从而实现 GPX4 的失活和铁突变的增强。此外,由于 mFe3O4 和 PDA 外壳具有显著的光热转换性能,PTT 进一步协同增强了 CDT 的功效,促进了铁跃迁。体内和体外实验均证实,这种协同疗法可以达到很好的肿瘤抑制效果:纳米治疗平台mFeB@PDA-FA可通过CDT、PTT和GSH消除的联合作用,有效破坏肿瘤细胞的氧化还原平衡,促进铁凋亡,为治疗对铁凋亡敏感的肿瘤提供了新的视角。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Augment of Ferroptosis with Photothermal Enhanced Fenton Reaction and Glutathione Inhibition for Tumor Synergistic Nano-Catalytic Therapy.

Introduction: Ferroptosis-driven tumor ablation strategies based on nanotechnology could be achieved by elevating intracellular iron levels or inhibiting glutathione peroxidase 4 (GPX4) activity. However, the intracellular antioxidative defense mechanisms endow tumor cells with ferroptosis resistance capacity. The purpose of this study was to develop a synergistic therapeutic platform to enhance the efficacy of ferroptosis-based tumor therapy.

Methods: In this study, a multifunctional nano-catalytic therapeutic platform (mFeB@PDA-FA) based on chemodynamic therapy (CDT) and photothermal therapy (PTT) was developed to effectively trigger ferroptosis in tumor. In our work, iron-based mesoporous Fe3O4 nanoparticles (mFe3O4 NPs) were employed for the encapsulation of L-buthionine sulfoximine (BSO), followed by the modification of folic acid-functionalized polydopamine (PDA) coating on the periphery. Then, the antitumor effect of mFeB@PDA-FA NPs was evaluated using Human OS cells (MNNG/HOS) and a subcutaneous xenograft model of osteosarcoma.

Results: mFe3O4 harboring multivalent elements (Fe2+/3+) could catalyze hydrogen peroxide (H2O2) into highly cytotoxic ˙OH, while the tumor microenvironment (TME)-responsive released BSO molecules inhibit the biosynthesis of GSH, thus achieving the deactivation of GPX4 and the enhancement of ferroptosis. Moreover, thanks to the remarkable photothermal conversion performance of mFe3O4 and PDA shell, PTT further synergistically enhanced the efficacy of CDT and facilitated ferroptosis. Both in vivo and in vitro experiments confirmed that this synergistic therapy could achieve excellent tumor inhibition effects.

Conclusion: The nanotherapeutic platform mFeB@PDA-FA could effectively disrupted the redox homeostasis in tumor cells for boosting ferroptosis through the combination of CDT, PTT and GSH elimination, which provided a new perspective for the treatment of ferroptosis sensitive tumors.

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来源期刊
International Journal of Nanomedicine
International Journal of Nanomedicine NANOSCIENCE & NANOTECHNOLOGY-PHARMACOLOGY & PHARMACY
CiteScore
14.40
自引率
3.80%
发文量
511
审稿时长
1.4 months
期刊介绍: The International Journal of Nanomedicine is a globally recognized journal that focuses on the applications of nanotechnology in the biomedical field. It is a peer-reviewed and open-access publication that covers diverse aspects of this rapidly evolving research area. With its strong emphasis on the clinical potential of nanoparticles in disease diagnostics, prevention, and treatment, the journal aims to showcase cutting-edge research and development in the field. Starting from now, the International Journal of Nanomedicine will not accept meta-analyses for publication.
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