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微细胞血素结合的阿普塔默:可逆纳米级抗凝剂

Alexander Roloff, Andrea S Carlini, Cassandra E Callmann

¹Department of Chemistry, Materials Science and Engineering, Biomedical Engineering, Northwestern University , Evanston, Illinois 60208, United States.

Journal of the American Chemical Society

|November 15, 2017

概括

新型的阿普坦胺形成纳米尺度,增强抗凝剂阿普坦胺的稳定性和循环时间,从而有效地抑制血栓形成. 这些状体提供了一个有前途的治疗方法,具有快速的可逆性.

科学领域:

生物化学
纳米技术
生物医学工程

背景情况:

体是具有特定结合能力的核酸配体.
通过向凝血级别酶,阿普塔默具有抗凝血剂的潜力.
自由体面临的挑战包括核酶降解和快速清除.

研究的目的:

开发稳定型的阿普坦基抗凝剂.
为了改善aptamers的药理动力学特性,用于体内应用.
制造出能够自组合成功能纳米结构的合物.

主要方法:

合成结血结合的两性体.
两动物自组成纳米级的聚合物.
在体外和体内评估细胞体结构,稳定性和抗凝剂活性.

主要成果:

在拥挤的环境中,小细胞体保留了本地二次结构.
对人血清中核酶的稳定性得到提高.
在体外有效抑制人体血凝固,并通过杂交快速逆转.
在体内血液循环时间延长的原因是细胞体的分子量和大小增加.

结论:

它们可以自组成稳定,功能性的纳米结构.
菌根性阿胺克服了自由阿胺的局限性,表现出更好的稳定性和药理动力学.
这一平台为开发包括抗凝固剂在内的基于aptamer的先进疗法提供了有前途的战略.

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