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反意义寡核酸嵌入式上下文响应性纳米颗粒来源于合成电离性脂质,用于lncRNA乳腺癌向治疗

Sourav Sarkar¹, Parikshit Moitra², Sayan Bera¹

¹School of Applied & Interdisciplinary Sciences, Indian Association for the Cultivation of Science, Kolkata 700032, India.

ACS applied materials & interfaces

|August 20, 2024

概括

研究人员开发了新的脂质纳米粒子 (LNP),用于非病毒输送反感性寡核酸 (ASO),向促进癌症的长非编码RNA (lncRNAs). 这种先进的系统有效地降低了lncRNA水平和瘤体积,提供了一个有前途的癌症治疗方法.

科学领域:

生物医学工程生物医学工程
分子生物学分子生物学
纳米技术纳米技术

背景情况:

长非编码RNAs (lncRNAs),包括HOTAIR和MALAT1,与癌症进展和患者预后不佳有关.
用反感性寡核酸 (ASO) 向 lncRNAs 是一种治疗策略,但高效的非病毒传递仍然是一个重大挑战.
在分娩期间保持ASO的结构和功能完整性对于治疗疗效至关重要.

研究的目的:

为先进的脂质纳米粒子 (LNP) 配方设计和合成新的可电离脂质.
开发一个响应上下文的LNP系统,以高效地非病毒传递 lncRNA向的ASO.
在体外和体内评估LNP介导的ASO输送对HOTAIR和MALAT1 lncRNAs的疗效.

主要方法:

合成具有多种头组的新型电离性脂质,用基于胆固醇的双胞胎酸性脂质和双胞胎酸性脂质配制成LNP.
使用生物分析技术调查LNP配方的上下文响应,以确定最佳配方.
在人癌细胞系中向HOTAIR lncRNA的ASOs的体外输送以及在小鼠模型中向MALAT1 lncRNA的ASOs的体外输送.

主要成果:

确定了一种优化的LNP配方,以实现ASO的高效和响应环境的交付.
在体外条件下观察到目标lncRNA水平 (HOTAIR和MALAT1) 的显著降低.
在体内实现了瘤体积的显著减少,证明了治疗潜力.

结论:

使用优化LNP进行非病毒基因传递的新型纳米材料系统已成功开发和验证.
开发的LNP系统有效地提供ASOs,以减少致癌的lncRNA表达并抑制瘤生长.
这项研究为 lncRNA 向癌症治疗提供了一个标准化和先进的平台.

关键词:

无意义的寡核酸 (ASO) 是一种无意义的寡核酸.语境响应能力响应能力在体内有效性 in vivo.长非编码RNA (lncRNA) 是一种长非编码RNA.合成的可电离性脂质纳米粒子 (LNP)

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