Carrier-free nanodrug based on small molecule drug and sonosensitizer for enhanced the ferroptosis-driven multimodal synergistic therapy of prostate cancer

IF 4.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutics and Biopharmaceutics Pub Date : 2025-02-03 DOI:10.1016/j.ejpb.2025.114656

Yao-Lin Wu, Rui-Rui Zhao, Xiao Wu, Chun-Lei Liu, Chun-Zhao Liu

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Abstract

Ferroptosis plays a significant role in overcoming the therapeutic resistance of cancer cells. Herein, a carrier-free nanoparticle based on small molecule drug sorafenib (SRF) and sonosensitizer rose bengal (RB) was constructed (named SR NPs) for ferroptosis-driven chemotherapy and sonodynamic synergistic therapy (SDT) of prostate cancer (PCa). SR NPs could be enriched in tumor cells and efficiently inhibit tumor cell proliferation. These nanodrugs could significantly reduce glutathione (GSH) synthesis, and inhibit glutathione peroxidase 4 (GPX4) expression by inhibiting the glutamate/cysteine antiporter system (System Xc^-) pathway of ferroptosis. Moreover, SR NPs-mediated ferroptosis significantly improved the amount of reactive oxygen species (ROS) generated by SDT, inhibited cell migration and adhesion, enhanced the accumulation of lipid peroxides (LPO) and augmented chemo-sonodynamic therapy. Notably, in vivo studies demonstrated that SR NPs enhanced tumor accumulation, exhibited good biocompatibility, and showed high anti-tumor efficacy in PC-3 tumor-bearing mice. This work offered a new strategy to enhance the treatment efficacy of prostate cancer (PCa) through ferroptosis-chemotherapy-sonodynamic synergistic therapy.

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基于铁下垂诱导剂和声敏剂的自组装纳米药物增强声动力触发多模态协同治疗前列腺癌。

铁下垂在克服癌细胞的治疗耐药中起着重要作用。本文以小分子药物索拉非尼（SRF）和声敏剂玫瑰红（RB）为基础，构建了一种无载体纳米颗粒（命名为SR NPs），用于前列腺癌（PCa）的铁致死化疗和声动力协同治疗（SDT）。SR NPs可在肿瘤细胞中富集，有效抑制肿瘤细胞增殖。这些纳米药物可以通过抑制铁死亡的谷氨酸/半胱氨酸反转运系统（system Xc-）途径，显著减少谷胱甘肽（GSH）的合成，抑制谷胱甘肽过氧化物酶4 （GPX4）的表达。此外，SR nps介导的铁凋亡显著提高了SDT产生的活性氧（ROS）的数量，抑制了细胞的迁移和粘附，增强了脂质过氧化物（LPO）的积累，增强了化学声动力治疗。值得注意的是，体内研究表明，SR NPs促进肿瘤积累，具有良好的生物相容性，并在PC-3荷瘤小鼠中表现出较高的抗肿瘤功效。本研究为通过吸铁-化疗-声动力协同治疗提高前列腺癌（PCa）的治疗效果提供了一种新的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Pharmaceutics and Biopharmaceutics 医学-药学

CiteScore

8.80

自引率

4.10%

发文量

211

审稿时长

36 days

期刊介绍： The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics. Topics covered include for example: Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids) Aspects of manufacturing process design Biomedical aspects of drug product design Strategies and formulations for controlled drug transport across biological barriers Physicochemical aspects of drug product development Novel excipients for drug product design Drug delivery and controlled release systems for systemic and local applications Nanomaterials for therapeutic and diagnostic purposes Advanced therapy medicinal products Medical devices supporting a distinct pharmacological effect.

文献相关原料

公司名称

产品信息

麦克林

1,3-diphenylisobenzofuran (DPBF)

麦克林

Rhodamine 123

阿拉丁

rose bengal (RB)

阿拉丁

2,7-dichloro-dihydro-fluorescein diacetate (DCFH-DA)