聚合诱导地位特异性干扰素α-块共聚合物的自组成具有显著增强药理性的菌体
Xinyu Liu1, Mengmeng Sun1, Jiawei Sun1
1Department of Biomedical Engineering, School of Medicine , Tsinghua University , Beijing 100084 , China.
Journal of the American Chemical Society
|August 8, 2018
概括
局部特异性局部聚合诱导自组合 (SI-PISA) 产生了干扰素-α (IFN) 结合. 这些小粒显著增强了蛋白质的生物活性和体内半衰期,导致小鼠的瘤完全抑制.
科学领域:
- 生物技术
- 聚合物化学
- 提供药物
背景情况:
- 蛋白质结合延长了治疗性蛋白质的半衰期,但通常会降低生物活性.
- 在半衰期延长期间开发维持蛋白质生物活性的策略对于有效的蛋白质疗法至关重要.
研究的目的:
- 开发一种新型的超分子自我组装策略,即局部聚合诱导自我组装 (SI-PISA),以克服与蛋白质半衰期延长相关的生物活性下降.
- 创建具有增强药理性能的干扰素-α (IFN) 结合.
主要方法:
- 使用SI-PISA从干扰素-α (IFN) 的C端生长了一种两块共聚物 (POEGMA-PHPMA).
- 这种现场聚合导致IFN-POEGMA-PHPMA结合细胞的形成.
主要成果:
- 与FDA批准的PEGASYS相比,IFN-POEGMA-PHPMA小粒在体外表现出21.5倍的生物活性.
- 与PEGASYS (49. 5小时) 和原生IFN (0. 8小时) 相比,微粒的半衰期显著延长 (83. 8小时).
- 在瘤模型中,微粒实现了完全的瘤抑制和100%的动物存活率,优于PEGASYS和IFN.
结论:
- SI-PISA是一种有前途的下一代技术,用于提高治疗蛋白质的药理性能.
- 这种方法有效地解决了蛋白质半衰期延长策略中生物活性降低的困境.
- 开发的结合细胞显示出改善癌症治疗和治疗需要蛋白质治疗的其他疾病的潜力.
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