| 叶鸣,王志刚,李兴升,李巧,牛诚诚,骆杰.包载经PEG修饰的重组腺病毒PLGA超声造影剂的制备及特性[J].中国医学影像技术,2010,26(11):2019~2022 |
| 包载经PEG修饰的重组腺病毒PLGA超声造影剂的制备及特性 |
| Preparation and characteristics of PEGylated recombinant adenovirus within PLGA ultrasound contrast agents |
| 投稿时间：2010-07-05 修订日期：2010-08-03 |
| DOI： |
| 中文关键词: 重组腺病毒 聚乙二醇修饰 超声微泡 造影剂 |
| 英文关键词:Recombinant adenoviruses PEGylated Ultrasound microbubbles Contrast media |
| 基金项目:国家自然科学基金青年科学基金(30800271)、国家自然科学基金面上项目(30770565)。 |
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| 中文摘要: |
| 目的 制备包载经聚乙二醇(PEG)修饰的重组腺病毒Ad-EGFP/HIF-1α高分子超声造影剂(PLGA),以改善腺病毒载体(Adv)在体内的安全性,提高Adv基因在细胞的转染效率。方法 使用活化的甲氧基PEG对重组Adv衣壳蛋白质进行修饰得到PEG化Adv(PEG-Adv),用双乳化法制备载PEG-Adv高分子超声造影剂(PLGA),观测其粒径、包封率、释放规律及释放病毒的活性,并检测其在巨噬细胞中的免疫反应程度。结果 PLGA分布均匀,平均粒径为6.23 μm;包封率为17.23%;PEG-Adv和单纯Adv从PLGA释放规律相似,但从PLGA释放出来的PEG-Adv的转染效率比从PLGA释放出来的单纯Adv高;包载PEG-Adv的PLGA产生的免疫反应强度也较低。结论 用PLGA微球包载PEG化的重组腺病毒Ad-EGFP/HIF-1α,可改善Adv在体内安全性差的缺点,释放出来的病毒稳定性好,转染效率较高,作为心血管疾病的基因治疗载体具有较好的研究前景。 |
| 英文摘要: |
| Objective To prepare PEGylated recombinant adenovirus for microencapsulation within poly lactic-co-glycolic acid (PLGA) ultrasound contrast agents,in order to alleviate the safety problems and increasing gene transfection efficiency of adenovirus vector (Adv) at a target tissue site. Methods PEGylated Adv (PEG-Adv) was constructed by PEGylated adenoviral capsid proteins with activated methoxypolyethylene glycols. Then the recombinant adenovirus was encapsulated in PLGA using a water-in-oil-in-water (W/O/W) double emulsion and solvent evaporation method. The diameter, capsulated efficiency, release test and the bioactivity of viruses incorporated in vitro were studied, and the relative extent of the immune response for Adv and PEG-Adv encapsulated within PLGA microspheres was analyzed using macrophage cells. Results The mean diameter of PLGA carrying PEG-Adv was 6.23 μm. More than 17.23% of adenovirus was encapsulated in PLGA. Adv and PEG-Adv were both released from PLGA similarly in a sustained fashion. However, PEG-Adv microspheres demonstrated a higher GFP gene transfection efficiency than Adv microspheres released from PLGA. The PEG-Adv micropheres also exhibited a reduced extent of innate immune response for macrophage cells. Conclusion PEG-Adv can be formulated within PLGA increasing gene transfection efficiency and safety, which can be ideal gene therapy vectors for cardiovascular disease in future. |
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