Enzyme-triggered PEGylated siRNA-nanoparticles for controlled release of siRNA
Enzyme-triggered PEGylated siRNA-nanoparticles for controlled release of siRNA
复制标题
DOI：
--
复制
发表时间：
2014-01
期刊：
影响因子：
--
通讯作者：
P. Yingyuad;M. Mével;C. Prata;C. Kontogiorgis;M. Thanou;Andrew D. Miller
中科院分区：
文献类型：
--
作者：
P. Yingyuad;M. Mével;C. Prata;C. Kontogiorgis;M. Thanou;Andrew D. Miller
我们最近的研究工作的一个关键目标是开发具有体内真实的潜在效用的新型“可降解纳米颗粒”系统。这些被设计为从给药点直到到达感兴趣的靶位点是稳定的，然后通过局部内源性条件的变化或通过施加一些外源性刺激来触发治疗剂有效载荷在靶位点的受控释放。在这里，我们描述了使用酶通过酶辅助纳米颗粒可降解性的过程来触发RNAi介导的治疗的调查。我们的方法是使用具有对肿瘤定位的弹性蛋白酶或基质金属蛋白酶-2消化敏感的肽基部分的PEG 2000-肽基脂质，并从这些制备推定的酶触发的PEG化siRNA纳米颗粒。我们的研究结果提供了初步的体外概念验证。从这些数据中，我们提出，这一概念应适用于功能性递送治疗性核酸的肿瘤细胞在体内，虽然酶辅助纳米粒子的可植入性的机制仍有待充分的特点。
A key goal of our recent research efforts has been to develop novel ‘triggerable nanoparticle’ systems with real potential utility in vivo. These are designed to be stable from the point of administration until a target site of interest is reached, then triggered for the controlled release of therapeutic agent payload(s) at the target site by changes in local endogenous conditions or through the application of some exogenous stimulus. Here we describe investigations into the use of enzymes to trigger RNAi-mediated therapy through a process of enzyme-assisted nanoparticle triggerability. Our approach is to use PEG2000-peptidyl lipids with peptidyl moieties sensitive to tumour-localized elastase or matrix metalloproteinase-2 digestion, and from these prepare putative enzyme-triggered PEGylated siRNA-nanoparticles. Our results provide initial proof of concept in vitro. From these data, we propose that this concept should be applicable for functional delivery of therapeutic nucleic acids to tumour cells in vivo, although the mechanism for enzyme-assisted nanoparticle triggerability remains to be fully characterized.