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iRGD修饰的细胞结合膜囊泡(iRGD-CBMVs)作为新型药物载体的增强抗肿瘤疗效

Enhanced Anti-Tumour Efficacy of iRGD-Modified Cell-Bound Membrane Vesicles (iRGD-CBMVs) as a Novel Drug Carrier.

作者信息

Zhao Haonan, Huang Zhendong, Sheng Qinghua, Shao Wenxiang, Zeng Min, Wang Kun, Zhang Yang, Qin Ying, Xiong Zhihao, Chen Lizhen, Wang Huaying, Rong Tong, Qiu Zhitao, Zhuang Hongda, Wu Zhiwen, Zhang Yuan, Zhang Wendiao, Chen Yong

机构信息

Institute for Advanced Study Nanchang University Nanchang Jiangxi China.

School of Life Science Nanchang University Nanchang Jiangxi China.

出版信息

J Extracell Biol. 2025 Jun 2;4(6):e70052. doi: 10.1002/jex2.70052. eCollection 2025 Jun.

DOI:10.1002/jex2.70052
PMID:40458672
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12127665/
Abstract

Cancer continues to be the foremost cause of mortality in humans. Persistent challenges in cancer treatment include inadequate drug targeting, severe toxicological side effects and uncontrolled drug distribution. The bioinspired membrane vesicle drug delivery systems have been emerging as promising therapeutic strategies. This study characterises unique cell-bound membrane vesicles (CBMVs), which are impervious to standard cleaning agents and effectively loaded with doxorubicin (DOX). For the first time, we used iRGD peptide to modify the CBMVs to enhance the CBMVs' targeting capabilities for cancer cells. Laser confocal microscopy and H Nuclear Magnetic Resonance Spectra (H NMR) have confirmed the CBMVs' iRGD modification and effective encapsulation with DOX (iRGD-CBMVs-DOX). Then, we used the iRGD-CBMVs-DOX to treat tumour cell lines and tumour-bearing mouse models. Our research identified that iRGD-CBMVs-DOX proves effective in inhibiting cell growth and migration for tumour cell lines, significant anti-tumour ability, reduced organ toxicity and continuous drug administration were revealed in tumour-bearing mouse models. Additionally, the iRGD-CBMVs-DOX demonstrated sustained drug release, indicating their potential for prolonged circulation. These findings are pivotal in enhancing cancer treatment through novel nanomedicine strategies, and highlight the potential of iRGD-modified vesicles (e.g., iRGD-CBMVs) as efficient drug carriers, contributing to targeted and biocompatible drug delivery advancements for cancer treatment.

摘要

癌症仍然是人类死亡的首要原因。癌症治疗中持续存在的挑战包括药物靶向性不足、严重的毒理学副作用和药物分布不受控制。受生物启发的膜泡药物递送系统已成为有前景的治疗策略。本研究对独特的细胞结合膜泡(CBMV)进行了表征,这些膜泡对标准清洁剂具有抗性,并有效地负载了阿霉素(DOX)。我们首次使用iRGD肽修饰CBMV,以增强其对癌细胞的靶向能力。激光共聚焦显微镜和氢核磁共振谱(H NMR)证实了CBMV的iRGD修饰以及与DOX的有效包封(iRGD-CBMV-DOX)。然后,我们使用iRGD-CBMV-DOX治疗肿瘤细胞系和荷瘤小鼠模型。我们的研究发现,iRGD-CBMV-DOX在抑制肿瘤细胞系的细胞生长和迁移方面被证明是有效的,在荷瘤小鼠模型中显示出显著的抗肿瘤能力、降低的器官毒性和持续给药效果。此外,iRGD-CBMV-DOX表现出持续的药物释放,表明它们具有延长循环的潜力。这些发现对于通过新型纳米医学策略增强癌症治疗至关重要,并突出了iRGD修饰的囊泡(如iRGD-CBMV)作为高效药物载体的潜力,有助于推动癌症治疗中靶向和生物相容性药物递送的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c365/12127665/44db6ba1c12d/JEX2-4-e70052-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c365/12127665/38c815bb7dc0/JEX2-4-e70052-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c365/12127665/da2ee36c4513/JEX2-4-e70052-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c365/12127665/5bcecf269ed9/JEX2-4-e70052-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c365/12127665/2fb625d4d304/JEX2-4-e70052-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c365/12127665/8c4ea57ed531/JEX2-4-e70052-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c365/12127665/f8d48c7ce87c/JEX2-4-e70052-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c365/12127665/d87a3b7b90c1/JEX2-4-e70052-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c365/12127665/ef2bef855024/JEX2-4-e70052-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c365/12127665/44db6ba1c12d/JEX2-4-e70052-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c365/12127665/38c815bb7dc0/JEX2-4-e70052-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c365/12127665/da2ee36c4513/JEX2-4-e70052-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c365/12127665/5bcecf269ed9/JEX2-4-e70052-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c365/12127665/2fb625d4d304/JEX2-4-e70052-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c365/12127665/8c4ea57ed531/JEX2-4-e70052-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c365/12127665/f8d48c7ce87c/JEX2-4-e70052-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c365/12127665/d87a3b7b90c1/JEX2-4-e70052-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c365/12127665/ef2bef855024/JEX2-4-e70052-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c365/12127665/44db6ba1c12d/JEX2-4-e70052-g006.jpg

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本文引用的文献

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Minimal Information for Studies of Extracellular Vesicles (MISEV): Ten-Year Evolution (2014-2023).细胞外囊泡研究的最低限度信息(MISEV):十年演变(2014 - 2023年)
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Tumor-penetrating iRGD facilitates penetration of poly(floxuridine-ketal)-based nanomedicine for enhanced pancreatic cancer therapy.
肿瘤穿透性iRGD促进基于聚(氟尿苷-缩酮)的纳米药物渗透,以增强胰腺癌治疗效果。
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Enhanced Tumor Targeting and Penetration of Proteolysis-Targeting Chimeras through iRGD Peptide Conjugation: A Strategy for Precise Protein Degradation in Breast Cancer.通过 iRGD 肽缀合增强蛋白水解靶向嵌合体的肿瘤靶向和穿透:乳腺癌中精确蛋白降解的策略。
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Doxorubicin and other anthracyclines in cancers: Activity, chemoresistance and its overcoming.多柔比星和其他蒽环类药物在癌症中的应用:活性、化学耐药性及其克服。
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