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人血浆来源的外泌体:一种用于递送羟基脲以对抗乳腺癌的有前景的载体系统。

Human Plasma-Derived Exosomes: A Promising Carrier System for the Delivery of Hydroxyurea to Combat Breast Cancer.

作者信息

Khalid Wajeeha, Aslam Afeefa, Ahmed Nadeem, Sarfraz Muhammad, Khan Jawad Akbar, Mohsin Sabeeh, Rajoka Muhammad Shahid Riaz, Nazir Imran, Amirzada Muhammad Imran

机构信息

Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Abbottabad, 22060, Pakistan.

Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, 54000, Pakistan.

出版信息

AAPS PharmSciTech. 2025 Jan 22;26(1):42. doi: 10.1208/s12249-024-03028-w.

DOI:10.1208/s12249-024-03028-w
PMID:39843767
Abstract

The aim of the present study was to investigate the potential of human plasma derived exosomes for the delivery of hydroxyurea to enhance its therapeutic efficacy in breast cancer. Plasma derived exosomes were isolated using differential centrifugation along with ultrafiltration method. Hydroxyurea was encapsulated in exosomes using a freeze-thaw method. The exosomes and Exo-HU were characterized for their size distribution, drug entrapment efficiency, in-vitro drug release profile, morphological analysis and cytotoxic effects on MCF-7 cell line. The results showed a mean size of 178.8 nm and a zeta potential of -18.3 mV, indicating good stability and 70% encapsulation effectiveness for HU. Exo-HU produced sustained drug release action with a considerable percentage released within 72 h. The morphological analysis indicated that the plasma derived exosomes were spherical, and cup shaped. In cytotoxicity studies on MCF-7 cells, Exo-HU has reduced cell viability compared to HU and blank exosomes. Findings of this study showed that human plasma-derived exosomes have been considered as effective delivery vehicle for hydroxyurea, potentially improving breast cancer treatment outcomes.

摘要

本研究的目的是探讨人血浆来源的外泌体用于递送羟基脲以增强其在乳腺癌治疗中的疗效的潜力。采用差速离心结合超滤法分离血浆来源的外泌体。使用冻融法将羟基脲包封在外泌体中。对外泌体和Exo-HU进行了大小分布、药物包封效率、体外药物释放曲线、形态分析以及对MCF-7细胞系的细胞毒性作用的表征。结果显示平均大小为178.8nm,zeta电位为-18.3mV,表明具有良好的稳定性,且羟基脲的包封效率为70%。Exo-HU产生持续的药物释放作用,在72小时内有相当比例的药物释放。形态分析表明血浆来源的外泌体呈球形和杯状。在对MCF-7细胞的细胞毒性研究中,与羟基脲和空白外泌体相比,Exo-HU降低了细胞活力。本研究结果表明,人血浆来源的外泌体被认为是羟基脲的有效递送载体,可能改善乳腺癌的治疗效果。

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本文引用的文献

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Regulation of exosomes as biologic medicines: Regulatory challenges faced in exosome development and manufacturing processes.外泌体作为生物药物的监管:外泌体开发和生产过程中面临的监管挑战。
Clin Transl Sci. 2024 Aug;17(8):e13904. doi: 10.1111/cts.13904.
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Exosomes: a review of biologic function, diagnostic and targeted therapy applications, and clinical trials.外泌体:生物学功能、诊断和靶向治疗应用以及临床试验的综述。
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Extracellular vesicles and lipoproteins - Smart messengers of blood cells in the circulation.
细胞外囊泡与脂蛋白——循环中血细胞的智能信使
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Human plasma derived exosomes: Impact of active and passive drug loading approaches on drug delivery.人血浆来源的外泌体:主动和被动载药方法对药物递送的影响。
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Characterization of the Intracellular Acidity Regulation of Brain Tumor Cells and Consequences for Therapeutic Optimization of Temozolomide.脑肿瘤细胞的细胞内酸度调节特性及其对替莫唑胺治疗优化的影响
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Bleomycin loaded exosomes enhanced antitumor therapeutic efficacy and reduced toxicity.载博来霉素的外泌体增强了抗肿瘤治疗效果,降低了毒性。
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Evaluation of exosomes encapsulated recombinant Interleukin-29 for its in vitro anticancer studies.评估包裹重组白细胞介素-29 的外泌体用于体外抗癌研究。
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