{"title":"Lactoferrin Nanoparticle-Vanadium Complex: A Promising High-Efficiency Agent against Glioblastoma by Triggering Autophagy and Ferroptosis","authors":"Shuangshuang Gai, Qiwei Yan, Shan Li, Xuwei Zhong, Yiming Qin, Ming Jiang","doi":"10.1021/acs.jmedchem.4c02696","DOIUrl":null,"url":null,"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.","PeriodicalId":46,"journal":{"name":"Journal of Medicinal Chemistry","volume":"2 1","pages":""},"PeriodicalIF":6.8000,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1021/acs.jmedchem.4c02696","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
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.
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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