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聚（N-乙烯基吡咯烷酮）-嵌段-聚（ε-己内酯）纳米颗粒高效递送熊果酸用于体外和体内抑制肝细胞癌生长

Efficient delivery of ursolic acid by poly(N-vinylpyrrolidone)-block-poly (ε-caprolactone) nanoparticles for inhibiting the growth of hepatocellular carcinoma in vitro and in vivo.

作者信息

Zhang Hao, Zheng Donghui, Ding Jing, Xu Huae, Li Xiaolin, Sun Weihao

机构信息

Department of Geriatric Gastroenterology, First Affiliated Hospital with Nanjing Medical University, Nanjing, People's Republic of China.

Department of Nephrology, Huai'an Hospital Affiliated with Xuzhou Medical College and Huai'an Second Hospital, Huai'an, People's Republic of China.

出版信息

Int J Nanomedicine. 2015 Mar 11;10:1909-20. doi: 10.2147/IJN.S77125. eCollection 2015.

DOI:10.2147/IJN.S77125
PMID:25792825
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4362907/
Abstract

Previous reports have shown that ursolic acid (UA), a pentacyclic triterpenoid derived from Catharanthus trichophyllus roots, could inhibit the growth of a series of cancer cells. However, the potential for clinical application of UA is greatly hampered by its poor solubility, whereas the hydrophobicity of UA renders it a promising model drug for nanosized delivery systems. In the current study, we loaded UA into amphiphilic poly(N-vinylpyrrolidone)-block-poly (ε-caprolactone) nanoparticles and performed physiochemical characterization as well as analysis of the releasing capacity. In vitro experiments indicated that UA-NPs inhibited the growth of liver cancer cells and induced cellular apoptosis more efficiently than did free UA. Moreover, UA-NPs significantly delayed tumor growth and localized to the tumor site when compared with the equivalent dose of UA. In addition, both Western blotting and immunohistochemistry suggested that the possible mechanism of the superior efficiency of UA-NPs is mediation by the regulation of apoptosis-related proteins. Therefore, UA-NPs show potential as a promising nanosized drug system for liver cancer therapy.

摘要

先前的报道表明，熊果酸（UA）是一种从长春花毛状根中提取的五环三萜类化合物，能够抑制一系列癌细胞的生长。然而，UA的临床应用潜力因其溶解度差而受到极大阻碍，而UA的疏水性使其成为纳米给药系统中一种有前景的模型药物。在本研究中，我们将UA负载到两亲性聚（N-乙烯基吡咯烷酮）-嵌段-聚（ε-己内酯）纳米颗粒中，并进行了理化性质表征以及释放能力分析。体外实验表明，UA纳米颗粒比游离UA更有效地抑制肝癌细胞的生长并诱导细胞凋亡。此外，与等量的UA相比，UA纳米颗粒显著延迟了肿瘤生长并定位于肿瘤部位。另外，蛋白质印迹法和免疫组织化学均表明，UA纳米颗粒具有更高效率的可能机制是通过调节凋亡相关蛋白来介导的。因此，UA纳米颗粒作为一种有前景的肝癌治疗纳米药物系统具有潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/57680491df41/ijn-10-1909Fig11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/2771f4f275de/ijn-10-1909Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/a9f15a844e4c/ijn-10-1909Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/884d6186a48c/ijn-10-1909Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/b5406c2e9640/ijn-10-1909Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/76ecf49fde03/ijn-10-1909Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/47851f3ea9c1/ijn-10-1909Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/efd68ad5d03e/ijn-10-1909Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/3ec1e310edd0/ijn-10-1909Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/22c63624e650/ijn-10-1909Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/afa356a97bc5/ijn-10-1909Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/57680491df41/ijn-10-1909Fig11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/2771f4f275de/ijn-10-1909Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/a9f15a844e4c/ijn-10-1909Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/884d6186a48c/ijn-10-1909Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/b5406c2e9640/ijn-10-1909Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/76ecf49fde03/ijn-10-1909Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/47851f3ea9c1/ijn-10-1909Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/efd68ad5d03e/ijn-10-1909Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/3ec1e310edd0/ijn-10-1909Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/22c63624e650/ijn-10-1909Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/afa356a97bc5/ijn-10-1909Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3968/4362907/57680491df41/ijn-10-1909Fig11.jpg

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