Lactoferrin Nanoparticle-Vanadium Complex: A Promising High-Efficiency Agent against Glioblastoma by Triggering Autophagy and Ferroptosis

IF 6.8 1区 医学 Q1 CHEMISTRY, MEDICINAL
Shuangshuang Gai, Qiwei Yan, Shan Li, Xuwei Zhong, Yiming Qin and Ming Jiang*, 
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Abstract

Glioblastoma represents the most aggressive type of brain cancer with minimal clinical advancements in recent decades attributed to the absence of efficient drug delivery strategies. In this study, we synthesized a series of vanadium complexes (V1–V4) and then constructed a lactoferrin (LF)-V4 nanoparticle (NP) delivery system. The nanoplatform crossed the blood-brain barrier by binding to low-density lipoprotein receptor-associated protein-1 and selectively targeted glioblastoma, ultimately inhibiting the growth of in situ glioblastoma tumors. LF-V4 NPs induced autophagic cell death in U87-MG cells by generating reactive oxygen species (ROS) that damaged the mitochondria. Further studies revealed that LF-V4 NPs triggered lipid peroxidation through the accumulation of ROS, the depletion of GSH, and the downregulation of GPX4 and SLC7A11, ultimately leading to ferroptosis in glioblastoma cells.

Abstract Image

乳铁蛋白纳米颗粒-钒复合物:一种有前途的高效抗胶质母细胞瘤剂,可触发自噬和铁凋亡
胶质母细胞瘤是最具侵袭性的脑癌类型,由于缺乏有效的药物输送策略,近几十年来临床进展甚微。在本研究中,我们合成了一系列钒配合物(V1-V4),并构建了乳铁蛋白(LF)-V4纳米颗粒(NP)递送体系。纳米平台通过与低密度脂蛋白受体相关蛋白-1结合,穿过血脑屏障,选择性靶向胶质母细胞瘤,最终抑制原位胶质母细胞瘤肿瘤的生长。LF-V4 NPs通过产生损伤线粒体的活性氧(ROS)诱导U87-MG细胞自噬死亡。进一步研究发现,LF-V4 NPs通过ROS的积累、GSH的消耗以及GPX4和SLC7A11的下调引发脂质过氧化,最终导致胶质母细胞瘤细胞铁凋亡。
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来源期刊
Journal of Medicinal Chemistry
Journal of Medicinal Chemistry 医学-医药化学
CiteScore
4.00
自引率
11.00%
发文量
804
审稿时长
1.9 months
期刊介绍: The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents. The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.
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