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载有冬凌草甲素的纳米颗粒通过调节ROS相关的Nrf2信号通路抑制乳腺癌进展。

Oridonin-Loaded Nanoparticles Inhibit Breast Cancer Progression Through Regulation of ROS-Related Nrf2 Signaling Pathway.

作者信息

Zhao Yue, Xiao Weiwei, Peng Wanqing, Huang Qinghua, Wu Kunru, Evans Colin E, Liu Xinguang, Jin Hua

机构信息

Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The Scientific Research Center of Dongguan, College of Pharmacy, Institute of Clinical Laboratory Medicine, Guangdong Medical University, Dongguan, China.

Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, China.

出版信息

Front Bioeng Biotechnol. 2021 Apr 7;9:600579. doi: 10.3389/fbioe.2021.600579. eCollection 2021.

DOI:10.3389/fbioe.2021.600579
PMID:33898397
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8058419/
Abstract

Oridonin (ORI) has been shown to inhibit tumor cell growth and proliferation , while its optimum anti-tumor activity is limited due to the poor aqueous solubility and bioavailability. In this study, to improve the bioavailability, we developed a nanoparticle-based drug delivery system to facilitate delivery of ORI to breast tumor. ORI was encapsulated in biodegradable nanoparticles (NPs) based on poly-lactic-co-glycolic acid (PLGA) and polyethylene glycol (PEG) to form ORI NPs (ORI-NPs). The resulting ORI-NPs exhibited a mean particle diameter of 100 nm and displayed an efficient cellular uptake by human breast cancer MCF-7 cells. Compared to free ORI that showed no effects on tumor cell proliferation, the ORI-NPs showed significant cytotoxicity and delayed endothelial cell migration, tube formation and angiogenesis. Pharmacokinetics studies showed that ORI-NPs significantly increased the half-life of ORI in the blood circulation. In the nude mouse xenograft model, ORI-NPs markedly inhibited tumor growth and angiogenesis, while ORI did not show any inhibitory effects on the growth of tumor xenografts. The mechanism experiments showed that the antitumor activity of ORI-NPs against breast cancer might be through ROS related Nrf2/HO-1 signaling pathway. Together, these results demonstrated that ORI-loaded PEG-PLGA NPs enhanced bioactivity and bioavailability over ORI, indicating that ORI-NPs may represent a promisingly effective candidate against breast cancer.

摘要

冬凌草甲素（ORI）已被证明可抑制肿瘤细胞的生长和增殖，但其最佳抗肿瘤活性因水溶性和生物利用度差而受到限制。在本研究中，为提高生物利用度，我们开发了一种基于纳米颗粒的药物递送系统，以促进ORI递送至乳腺肿瘤。ORI被包裹在基于聚乳酸-乙醇酸共聚物（PLGA）和聚乙二醇（PEG）的可生物降解纳米颗粒（NPs）中，形成ORI NPs（ORI-NPs）。所得的ORI-NPs平均粒径为100 nm，并显示出被人乳腺癌MCF-7细胞有效摄取。与对肿瘤细胞增殖无影响的游离ORI相比，ORI-NPs显示出显著的细胞毒性，并延迟了内皮细胞迁移、管腔形成和血管生成。药代动力学研究表明，ORI-NPs显著延长了ORI在血液循环中的半衰期。在裸鼠异种移植模型中，ORI-NPs显著抑制肿瘤生长和血管生成，而ORI对肿瘤异种移植的生长未显示任何抑制作用。机制实验表明，ORI-NPs对乳腺癌的抗肿瘤活性可能通过ROS相关的Nrf2/HO-1信号通路。总之，这些结果表明，负载ORI的PEG-PLGA NPs比ORI具有更高的生物活性和生物利用度，表明ORI-NPs可能是一种有前景的抗乳腺癌有效候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f32/8058419/1299c9ae37f4/fbioe-09-600579-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f32/8058419/3b31d63c0db5/fbioe-09-600579-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f32/8058419/625d5aafc659/fbioe-09-600579-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f32/8058419/e665078c34fe/fbioe-09-600579-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f32/8058419/83559cfea35a/fbioe-09-600579-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f32/8058419/bb27af55fe5e/fbioe-09-600579-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f32/8058419/fd70d3218b24/fbioe-09-600579-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f32/8058419/1299c9ae37f4/fbioe-09-600579-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f32/8058419/3b31d63c0db5/fbioe-09-600579-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f32/8058419/625d5aafc659/fbioe-09-600579-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f32/8058419/e665078c34fe/fbioe-09-600579-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f32/8058419/83559cfea35a/fbioe-09-600579-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f32/8058419/bb27af55fe5e/fbioe-09-600579-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f32/8058419/fd70d3218b24/fbioe-09-600579-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f32/8058419/1299c9ae37f4/fbioe-09-600579-g007.jpg

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