黄安皓,韩顺平,陆燕平,马瑞,郑杭生,李范珠
HUANG An-hao,HAN Shun-ping,LU Yan-ping,MA Rui,ZHENG Hang-sheng,LI Fan-zhu

• 1:浙江中医药大学药学院

摘要(Abstract)：

三氧化二砷(ATO)是中药砒霜的有效成分,已有研究表明其对多种肿瘤具有良好的生长抑制及促凋亡作用,但由于毒性大和透血脑屏障(BBB)难等问题严重限制了其在脑胶质瘤治疗方面的应用。聚酰胺-胺树状大分子(PAMAM)作为一种人工合成的高分子化合物,具有渗透性及稳定性强且生物相容性好等优点,且第5代PAMAM的空间结构更立体,是药物载体的理想选择。该课题采用RGDyC和PEG共同修饰第5代PAMAM,并通过核磁共振氢谱图证明了该纳米载体的成功合成;纳米粒度-电位分析仪和透射电镜图分析显示其平均粒径大约集中在20 nm左右;体外释放实验表明,该递药系统不仅具有缓释效果,同时还有一定的p H敏感特性;细胞结果显示,经RGDyC和PEG共修饰后的PAMAM与未经修饰组相比,细胞毒性显著降低,且该递药系统具有更好的体外跨血脑屏障(BBB)抗肿瘤效果,同时也进一步证明了RGDyC的肿瘤靶向作用。
Arsenic trioxide( ATO) is an effective component of traditional Chinese medicine arsenic. The existing studies have shown its good inhibition and apoptosis ability on a variety of tumours. However,its toxicity and difficulties in the permeability into the blood brain barrier( BBB) has the limitation in the application of glioma treatment. Polyamide-amine dendrimer( PAMAM) is a synthetic polymer with many advantages,such as a good permeability,stability and biocompatibility. Additionally,the 5 thgeneration of PAMAM is an ideal drug carrier due to its three-dimensional structure. In this study,the 5 thgeneration of PAMAM co-modified with RGDyC and PEG,then confirmed by1 H-NMR. The average particle size of nanoparticles was about 20 nm according to the nanoparticle size-potential analyser and transmission electron microscopy. In vitro release showed that the nanocarrier not only has the sustained release effect,but also some p H-sensitive properties. The cell results showed that PAMAM co-modified with RGDyC and PEGAM has a lower cytotoxicity than the non-modified group in vitro. Accordingly,the drug delivery system has a better anti-tumour effect across the blood brain barrier(BBB) in vitro,which further proves the tumour targeting of RGDyC.

关键词(KeyWords)： 三氧化二砷;PAMAM;RGDyC;聚乙二醇;脑胶质瘤;血脑屏障
arsenic trioxide;PAMAM;RGDyC;polyethylene glycol;glioma;blood brain barrier

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81473361,81673707,81603303);; 老年病中药新产品湖北省协同创新中心2015年建设专项(15111903)

作者(Author): 黄安皓,韩顺平,陆燕平,马瑞,郑杭生,李范珠
HUANG An-hao,HAN Shun-ping,LU Yan-ping,MA Rui,ZHENG Hang-sheng,LI Fan-zhu

DOI: 10.19540/j.cnki.cjcmm.20180117.010

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