胺修饰对三阴性乳腺癌治疗中氧化还原反应性聚乙二醇化两亲性胶束纳米颗粒siRNA递送的影响

Fatemeh Mehradnia, C. Alexander
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引用次数: 0

摘要

我们开发了一组含有不同类型胺连接剂的甲氧基聚乙二醇-共聚(N3-ε-己内酯)(mPEG-N3PCL)共聚物,并研究了所引入的胺连接剂对纳米粒子基因传递效率的影响。纳米颗粒通过氧化还原反应连接剂从己内酯区域交联。考察了包括氧化还原交联和氮磷比在内的配方变量,以获得最佳尺寸和最高siRNA捕获效率(EE)的纳米颗粒。采用dls和纳米滴紫外-可见光谱对纳米颗粒进行了表征。纳米颗粒的大小、多分散性指数和sirna的包封效果取决于所有被检测的配方变量,特别是氮磷比。优选出粒径为56.13 nm, EE为92.24%,N:P比为5的最佳配方。可控制的大小、装载效率和氧化还原反应的释放模式使这类新型载体成为肿瘤靶向基因递送应用的有希望的候选者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The effect of Amine modification on siRNA delivery of redox-responsive PEGylated amphiphilic micellar nanoparticles for triple negative breast cancer therapy
We developed a set of methoxypoly(ethyleneglycol)-co-poly(N3-ε-caprolactone) (mPEG-N3PCL)copolymers with different types of amine linkers and investigated thecontribution of the introduced amino linker to the gene delivery efficiency ofnanoparticles. The nanoparticles were crosslinked from the caprolactone regionswith a redox-responsive linker. Formulation variables including Redox-crosslinkingand N:P ratio were examined to obtain nanoparticles with optimal size andhighest siRNA entrapment efficacy (EE). The nanoparticles were characterized byDLS, and nanodrop UV-vis spectroscopy. Nanoparticle size, polydispersity index and siRNAentrapment efficacy were found to depend on the all the examined formulationvariables specially the N:P ratio. The formulation with N:P ratio of 5 with56.13 nm in size and 92.24% EE was chosen as the optimal formulation.Controllable size, loading efficiency and releasepattern by redox-responsivity make this class of novel carriers a promisingcandidate for tumour targeted gene delivery applications. 
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