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溶酶体的磁调控在癌症治疗中的应用。

Magnetic modulation of lysosomes for cancer therapy.

机构信息

Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, School of Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, Tongji University, Shanghai, China.

Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

出版信息

Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2024 Mar-Apr;16(2):e1947. doi: 10.1002/wnan.1947.

Abstract

Lysosomes play a central role in biochemical signal transduction and oxidative stress in cells. Inducing lysosome membrane penetration (LMP) to cause lysosomal-dependent cell death (LCD) in tumor cells is an effective strategy for cancer therapy. Chemical drugs can destroy the stability of lysosomes by neutralizing protons within the lysosomes or enhancing the fragility of the lysosomal membranes. However, there remain several unsolved problems of traditional drugs in LMP induction due to insufficient lysosomal targeting, fast metabolism, and toxicity in normal cells. With the development of nanotechnology, magnetic nanoparticles have been demonstrated to target lysosomes naturally, providing a versatile tool for lysosomal modulation. Combined with excellent tissue penetration and spatiotemporal manipulability of magnetic fields, magnetic modulation of lysosomes progresses rapidly in inducing LMP and LCD for cancer therapy. This review comprehensively discussed the strategies of magnetic modulation of lysosomes for cancer therapy. The intrinsic mechanisms of LMP-induced LCD were first introduced. Then, the modulation of lysosomes by diverse physical outputs of magnetic fields was emphatically discussed. Looking forward, this review will shed the light on the prospect of magnetic modulation of lysosomes, inspiring future research of magnetic modulation strategy in cancer therapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

摘要

溶酶体在细胞中的生化信号转导和氧化应激中发挥着核心作用。诱导溶酶体膜通透性(LMP)以引起肿瘤细胞中的溶酶体依赖性细胞死亡(LCD)是癌症治疗的有效策略。化学药物可以通过中和溶酶体内的质子或增强溶酶体膜的脆弱性来破坏溶酶体的稳定性。然而,由于传统药物在溶酶体靶向性、代谢速度快和正常细胞毒性方面存在不足,在 LMP 诱导方面仍存在一些未解决的问题。随着纳米技术的发展,磁性纳米颗粒已被证明可以自然靶向溶酶体,为溶酶体调节提供了一种多功能工具。结合磁场的出色组织穿透性和时空可操作性,磁调节溶酶体在诱导 LMP 和 LCD 以用于癌症治疗方面取得了快速进展。本综述全面讨论了用于癌症治疗的溶酶体磁调节策略。首先介绍了 LMP 诱导的 LCD 的内在机制。然后,着重讨论了磁场的各种物理输出对溶酶体的调节。展望未来,本综述将为溶酶体的磁调节前景提供启示,激发癌症治疗中磁调节策略的未来研究。本文属于以下类别: 治疗方法和药物发现 > 新兴技术 治疗方法和药物发现 > 用于肿瘤疾病的纳米医学 纳米技术在生物学中的应用 > 生物学中的纳米级系统

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