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通过多种评估方法，使用生物可降解自组装胶束增强姜黄素的抗神经胶质瘤治疗作用。

Enhancing the anti-glioma therapy of doxorubicin by honokiol with biodegradable self-assembling micelles through multiple evaluations.

机构信息

Department of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation center, Chengdu, 610041, PR China.

Department of Pharmacology, Yale School of Medicine, Yale University, New Haven, Connecticut, 06520, USA.

出版信息

Sci Rep. 2017 Feb 27;7:43501. doi: 10.1038/srep43501.

DOI:10.1038/srep43501
PMID:28240249
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5327495/
Abstract

Combination chemotherapy is an important protocol in glioma therapy and honokiol shows synergistic anticancer effects with doxorubicin. In this paper, honokiol (HK) and doxorubicin (Dox) co-loaded Methoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) nanoparticles were prepared with a assembly method. The particle size (about 34 nm), morphology, X-ray Powder Diffraction (XRD), in vitro release profile, cytotoxicity and cell proliferation effects were studied in detail. The results indicated that honokiol and doxorubicin could be efficiently loaded into MPEG-PCL nanoparticles simultaneously, and could be released from the micelles in an extended period in vitro. In addition, honokiol and doxorubicin loaded in MPEG-PCL nanoparticles could efficiently suppress glioma cell proliferation and induce cell apoptosis in vitro. Furthermore, Dox-HK-MPEG-PCL micelles inhibited glioma growth more significantly than Dox-MPEG-PCL and HK-MPEG-PCL in both nude mice and zebrafish tumor models. Immunohistochemical analysis indicated that DOX-HK-MPEG-PCL micelles improved Dox's anti-tumor effect by enhancing tumor cell apoptosis, suppressing tumor cell proliferation, and inhibiting angiogenesis. Our data suggest that Dox-HK-MPEG-PCL micelles have the potential to be applied clinically in glioma therapy.

摘要

联合化疗是神经胶质瘤治疗的重要方案，厚朴酚与阿霉素具有协同抗癌作用。本文采用自组装法制备了同时载药的厚朴酚（HK）和阿霉素（Dox）的甲氧基聚乙二醇-聚己内酯（MPEG-PCL）纳米粒，并对其粒径（约 34nm）、形态、X 射线粉末衍射（XRD）、体外释放特性、细胞毒性和细胞增殖作用进行了详细研究。结果表明，厚朴酚和阿霉素可以同时被高效地装载到 MPEG-PCL 纳米粒中，并可以在体外延长时间从胶束中释放。此外，载药 MPEG-PCL 纳米粒可以有效地抑制神经胶质瘤细胞的增殖并诱导细胞凋亡。此外，在裸鼠和斑马鱼肿瘤模型中，Dox-HK-MPEG-PCL 胶束比 Dox-MPEG-PCL 和 HK-MPEG-PCL 更显著地抑制了神经胶质瘤的生长。免疫组化分析表明，Dox-HK-MPEG-PCL 胶束通过增强肿瘤细胞凋亡、抑制肿瘤细胞增殖和抑制血管生成来提高 Dox 的抗肿瘤作用。我们的数据表明，Dox-HK-MPEG-PCL 胶束具有在神经胶质瘤治疗中临床应用的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/beabf1a4f51e/srep43501-f16.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/0a8add7fb91b/srep43501-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/51cc22e7b25f/srep43501-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/42ce8aef0c7a/srep43501-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/d605915c97a8/srep43501-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/acc13579b029/srep43501-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/91436765ed01/srep43501-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/043b52b04caa/srep43501-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/5bfb87221590/srep43501-f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/77179461e6d4/srep43501-f11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/c195155b65ca/srep43501-f12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/5bd1f17cbae8/srep43501-f13.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/3975c3171b33/srep43501-f14.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/966668d9561d/srep43501-f15.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/beabf1a4f51e/srep43501-f16.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/0a8add7fb91b/srep43501-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/424dfda1f08e/srep43501-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/6603317928c9/srep43501-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/51cc22e7b25f/srep43501-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/42ce8aef0c7a/srep43501-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/d605915c97a8/srep43501-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/acc13579b029/srep43501-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/91436765ed01/srep43501-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/043b52b04caa/srep43501-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/5bfb87221590/srep43501-f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/77179461e6d4/srep43501-f11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/c195155b65ca/srep43501-f12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/5bd1f17cbae8/srep43501-f13.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/3975c3171b33/srep43501-f14.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/966668d9561d/srep43501-f15.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/758a/5327495/beabf1a4f51e/srep43501-f16.jpg

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