生物素介导的胰腺癌靶向聚合物胶束制备及其用于光动力治疗的初步研究

发布时间：2018-02-17 09:06

本文关键词： 生物素聚合物胶束竹红菌乙素肿瘤靶向光动力治疗　出处：《药学学报》2015年08期 　论文类型：期刊论文

【摘要】：本文探索以生物素为导向分子介导纳米载体靶向胰腺癌并开展光动力治疗的可行性。以聚乙二醇-磷脂酰乙醇胺[poly(ethylene glycol)-distearoyl phosphatidyl ethanolamine,m PEG2000-DSPE]为载体材料,生物素-聚乙二醇-磷脂酰乙醇胺[biotin-poly(ethylene glycol)-distearoyl phosphatidyl ethanolamine,Biotin-PEG3400-DSPE]为功能材料,通过薄膜水化法制备生物素修饰的聚合物胶束。通过体外细胞摄取实验和体内荧光活体成像实验考察其靶向性并对导向分子的比例进行优选。在此基础上,以新型光动力药物竹红菌乙素为光敏剂,制备载药胶束制剂并对其体内外药效进行系统评价。结果表明,5%(mol/mol)比例的生物素修饰具有相对较好的体内外靶向性,其载药制剂粒径较小[(36.74±2.16)nm]且分布较均一,药物的包封率较高,达到(80.06±0.19)%。药效评价显示,经生物素介导能提高光敏剂对Bx PC-3细胞的光毒性,在体内则表现为显著抑制裸鼠皮下瘤生长。本研究成功地将生物素介导主动靶向的"抑瘤谱"扩大至胰腺癌,所得载光敏剂胶束的制剂学性质较好,为胰腺癌尤其是部分难渗透、放化疗不敏感的胰腺癌治疗研究提供了有益的思路。
[Abstract]:The aim of this study was to explore the feasibility of targeting pancreatic cancer with biotin oriented molecules and developing photodynamic therapy with poly(ethylene glycol)-distearoyl phosphatidyl ethanolaminem PEG2000-DSPE. Biotin-poly(ethylene glycol)-distearoyl phosphatidyl ethanolamine (Biotin-PEG3400-DSPE) was used as functional material. Biotin-modified polymer micelles were prepared by membrane hydration. The targeting of biotinylated polymer micelles was investigated by in vitro cell uptake test and fluorescence imaging in vivo. A new photodynamic drug, Hypocrellin B, was used as Guang Min to prepare the micelle preparation and to evaluate its drug efficacy in vivo and in vitro. The results showed that the biotin modification with a ratio of 5mol / mol was relatively good in vitro and in vivo targeting. The size of the drug carrier was smaller [36.74 卤2.16 nm] and the distribution was uniform. The encapsulation efficiency of the drug was higher, reaching 80.06 卤0.190.The pharmacodynamics evaluation showed that the phototoxicity of Guang Min to Bx PC-3 cells could be enhanced by biotin mediated. In vivo, the growth of subcutaneous tumor in nude mice was significantly inhibited. In this study, the biotin mediated active targeting "inhibition spectrum" was successfully extended to pancreatic cancer. It provides a useful idea for the treatment of pancreatic cancer, especially for pancreatic cancer, which is difficult to penetrate and not sensitive to radiotherapy and chemotherapy.
【作者单位】：西南大学药学院;
【基金】：国家自然科学基金资助项目(21272187) 中央高校基本科研业务费资助项目(XDJK2013A015)
【分类号】：R943

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