All-stage targeted nanodiscs for glioma treatment by inducing cuproptosis and apoptosis of cancer cells and cancer stem cells

IF 11.9 1区医学 Q1 PHARMACOLOGY & PHARMACY

Asian Journal of Pharmaceutical Sciences Pub Date : 2024-12-17 DOI:10.1016/j.ajps.2024.101010

Yuan Ding , Ruohan Chen , Jianfen Zhou , Yanning Bao , Nana Meng , Xudong Zheng , Shengmin Yang , Jiasheng Lu , Zhixuan Jiang , Yu Liu , Cao Xie , Linwei Lu , Weiyue Lu

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Abstract

There remain several intractable challenges for chemotherapy in glioma treatment, including the blood-brain barrier (BBB), blood-brain tumor barrier (BBTB), and tumor heterogeneity caused by cancer stem cells (CSCs), which are resistant to conventional chemotherapy. Here, we established a nano strategy to kill glioma cells and CSCs, combining carfilzomib and bis(diethyldithiocarbamate)copper. The synergistic drug combination disturbed cell protein metabolism at different stages and induced apoptosis and cuproptosis. The Y-shaped targeting ligand pHA-VAP-modified nanodiscs were designed to help the chemotherapeutic agents cross the BBB/BBTB and finally accumulate in tumor site. This all-stage targeting and all-stage treatment nanomedicine significantly prolonged the survival in glioma-bearing mice and might inspire the rational design of advanced drug delivery platforms.

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靶向纳米片通过诱导肿瘤细胞和肿瘤干细胞的铜增生和凋亡来治疗胶质瘤

化疗在胶质瘤治疗中仍然存在一些棘手的挑战，包括血脑屏障（BBB）、血脑肿瘤屏障（BBTB）和肿瘤干细胞（CSCs）引起的肿瘤异质性，这些对传统化疗具有耐药性。在这里，我们建立了一种纳米策略来杀死胶质瘤细胞和CSCs，结合卡非佐米和双（二乙基二硫代氨基甲酸盐）铜。协同用药干扰不同阶段细胞蛋白代谢，诱导细胞凋亡和铜坏死。设计了y形靶向配体pha - vap修饰的纳米圆盘，帮助化疗药物穿过血脑屏障/血脑屏障，最终在肿瘤部位积累。这种全阶段靶向、全阶段治疗的纳米药物显著延长了胶质瘤小鼠的生存期，并可能启发先进给药平台的合理设计。

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来源期刊

Asian Journal of Pharmaceutical Sciences Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

CiteScore

18.30

自引率

2.90%

发文量

审稿时长

14 days

期刊介绍： The Asian Journal of Pharmaceutical Sciences (AJPS) serves as the official journal of the Asian Federation for Pharmaceutical Sciences (AFPS). Recognized by the Science Citation Index Expanded (SCIE), AJPS offers a platform for the reporting of advancements, production methodologies, technologies, initiatives, and the practical application of scientific knowledge in the field of pharmaceutics. The journal covers a wide range of topics including but not limited to controlled drug release systems, drug targeting, physical pharmacy, pharmacodynamics, pharmacokinetics, pharmacogenomics, biopharmaceutics, drug and prodrug design, pharmaceutical analysis, drug stability, quality control, pharmaceutical engineering, and material sciences.