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重定位抗胺剂埃巴斯作为细胞内siRNA递送增强剂

Cristina Muntean¹, Eva Blondeel², Laure Harinck¹

¹Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium.

International journal of pharmaceutics

|August 26, 2023

概括

乙巴斯是一种抗胰岛素,显著增强了小干扰RNA (siRNA) 输送到癌细胞中的作用. 这增强了基因沉默疗法,改善了非小细胞肺癌的治疗结果.

科学领域:

药理学药理学是指药理学的学科.
分子生物学分子生物学
癌症治疗方法癌症治疗方法

背景情况:

小干扰RNAs (siRNAs) 是强大的基因沉默剂,但需要高效的细胞质递送才能获得治疗效果.
目前的siRNA传递方法往往无法逃离内体,导致溶酶体降解和降低有效性.
阴阳性两性药物 (CAD) 可以通过透内体/溶体膜来增强细胞质的传递.

研究的目的:

评估抗素CAD的ebastine,作为非小细胞肺癌 (NSCLC) 中siRNA传递和基因沉默的潜在增强剂.
将ebastine的疗效与其他CAD进行比较,并评估其与各种siRNA配方的性能.

主要方法:

在2D和3DNSCLC模型中使用聚合纳米凝和胆固醇结合siRNA研究了ebastine对siRNA传递的影响.
评估了ebastine对具有特定脂质和PEGylation特征的脂质纳米粒子 (LNP) 配方的影响.
量化siRNA介导的基因沉默效率和基因淘汰.

主要成果:

埃巴斯提高了聚合物纳米凝的siRNA介导基因沉默效率40倍.
埃巴斯在2D培养物和3D瘤球体中显著增强了胆固醇结合siRNA的基因淘汰.
埃巴斯证明了对先进的LNP配方的siRNA传递的强有力的增强,性能优于当前的标准.

结论:

埃巴斯被认为是癌细胞中siRNA传递的高效和多功能增强剂.
埃巴斯能够改善siRNA的细胞质释放,这在瘤学中是一个有前途的组合治疗策略.
这一发现为开发更有效的基于siRNA的癌症治疗开辟了新的途径.

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