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通过在脂质纳米颗粒中共同封装甘他素以有效的siRNA传递和癌症治疗来破坏内体细胞

Ning Yang^1,2,3, Qi Sun^1,2,3, Yaoqi Wang^1,2,3

¹School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China.

Asian journal of pharmaceutical sciences

|June 9, 2025

概括

这项研究开发了新的脂质纳米颗粒 (LNP),共同提供小干扰RNA (siRNA) 和 gentamicin (GM),以增强癌症治疗. 这些纳米颗粒有效地促进siRNA内体逃生,从而改善了基因沉默和显著的瘤生长抑制.

科学领域:

生物医学工程生物医学工程
纳米技术纳米技术
癌症治疗癌症治疗

背景情况:

治疗疾病的有效siRNA传递受到内溶酶体捕获的阻碍.
传统的纳米颗粒很难有效地释放它们的有效载荷从内溶解体.

研究的目的:

用小分子药物开发一种用于增强siRNA内溶体释放的新策略.
为了研究联合输送的siRNA和 gentamicin (GM) 的协同效应,以改善癌症治疗.

主要方法:

在Onpattro®配方中封装 gentamicin (GM),以创建 LNP-siRNA/GM纳米粒子.
评估siRNA内溶体逃生机制,包括内破坏,ROS诱导和脂积累.
在小鼠中评估mRNA-EGFR沉默效率,细胞生物活动和体内瘤生长抑制.

主要成果:

通过内体破坏,LNP-siRNA/GM纳米颗粒有效促进了siRNA的内溶酶体逃逸.
实现了~81%的mRNA-EGFR沉默,明显高于单独的LNP-siEGFR (~56.23%).
在HepG2细胞中表现出协同作用的抗癌作用,并在体内显著抑制瘤生长.

结论:

使用LNPs的GM和siRNA的同时输送提供了一种有效的策略,可以克服内分体捕获.
这种方法显著增强了基因淘汰,并改善了癌症治疗结果.
开发的LNP-siRNA/GM系统对各种基于LNP的siRNA传递应用具有前景.

关键词:

癌症治疗治疗癌症治疗肠内体破坏肠内体破坏这是一种 gentamicin.号发送送货的时间

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