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使用带有2-氨酸碳化基组的两性聚合物进行选择性附着的蛋白质的细胞溶液输送
Rapeepat Sangsuwan, Phum Tachachartvanich, Matthew B Francis1
1Materials Sciences Division , Lawrence Berkeley National Laboratories , Berkeley , California 94720 , United States.
Journal of the American Chemical Society
|January 22, 2019
概括
研究人员开发了一种新的生物结合方法, 这种方法成功地将功能性蛋白质运送到细胞质中,从而增强其治疗癌症的潜力.
科学领域:
- 生物结合化学
- 分子输送系统
- 癌症治疗方法
背景情况:
- 蛋白质疗法具有显著的潜力,但由于膜透性差,细胞内传递面临挑战.
- 目前的方法往往导致内体捕获,限制细胞内输送蛋白质的有效性.
- 需要有效的策略来将功能性蛋白质运输到细胞细胞质中以进行向治疗.
研究的目的:
- 开发一种新的生物结合策略,用于将两聚合物选择性地附着在蛋白质上.
- 能够有效地将功能性蛋白质输送到细胞质中.
- 评估聚合物结合蛋白在癌细胞中的治疗潜力.
主要方法:
- 在温和的水性条件下,选择性地将两性聚合物附加到蛋白质的N端,使用2-氨酸碳化物组.
- 使用成像研究来追踪各种癌症细胞系中的聚合物-蛋白质结合物的细胞内传递.
- 在细胞内输送后评估修饰的核糖酶A (RNase A) 的保留活性和细胞毒性作用.
主要成果:
- 建立了一个简单的,基于生物结合的方法,用于将聚合物连接到无遗传修饰的蛋白质.
- 证实了聚合物-蛋白质结合物的成功输入多种癌细胞系的细胞质,可能是通过膜融合.
- 结合RNase A保持其活性,并在细胞溶液输送时显示出癌细胞中增强的细胞毒性.
结论:
- 这种生物结合方法为基于蛋白质的细胞内治疗提供了一个有前途的平台.
- 这种方法克服了内体捕获,增加了治疗蛋白质在细胞内点的有效度.
- 聚合物结合RNase A的已证明的疗效突显了开发基于蛋白质的新型癌症疗法的潜力.
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