索诺PIN可实现PROTACs的精确,非侵入性和高效的细胞内输送
Yuqi Wu1, Mingyuan Liu2, Ke Li1
1Thomas Lord Department of Mechanical Engineering and Materials Science, Duke University, Durham, NC 27708.
概括
超声波辅助精确细胞内纳米递送 (SonoPIN) 通过使用超声波将向蛋白解酶的仿真体 (PROTACs) 送入癌细胞,从而增强癌症治疗. 这种有针对性的方法最大限度地降低了毒性,并有效降解了促进癌症的蛋白质.
科学领域:
- 生物医学工程 生物医学工程
- 纳米技术纳米技术
- 在瘤学瘤学.
背景情况:
- 针对蛋白质分解的嵌合体 (PROTACs) 显示出癌症治疗的前景,但面临着交付挑战.
- 细胞透性差,细胞内吸收和目标外毒性限制PROTAC的临床翻译.
- 针对性降解瘤原蛋白对于有效的癌症治疗至关重要.
研究的目的:
- 开发一种创新的纳米输送系统,用于增强PROTACs的细胞内输送.
- 为了克服传统的PROTAC交付方法的局限性.
- 为了证明有针对性的癌细胞降解和亡诱导与最小的非目标效应.
主要方法:
- 开发的超声波辅助精确细胞内纳米输送 (SonoPIN),一个超声驱动的,aptamer引导的微泡系统.
- 使用阿普坦胺结合的微气泡和超声波诱导的声波穿用于向细胞膜透.
- 在癌细胞模型中使用光标记的PROTACs准BRD4.
主要成果:
- 在超声波刺激60秒内,SonoPIN实现了细胞内PROTAC输送的7倍增加.
- 向癌细胞显示BRD4蛋白水平降低了70%.
- 非癌细胞表现出无法检测的BRD4降解,生存率超过99%.
结论:
- 索诺宾使得PROTACs的高效和选择性细胞内传递成为可能.
- 该系统有效地诱导癌细胞亡,同时保持非目标细胞的活力.
- 在癌症治疗中,SonoPIN代表了一个有前途的非侵入性平台,用于向的PROTAC输送.
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