Enzyme-triggered PEGylated pDNA-nanoparticles for controlled release of pDNA in tumors.
Enzyme-triggered PEGylated pDNA-nanoparticles for controlled release of pDNA in tumors.
复制标题
酶触发的聚乙二醇化 pDNA 纳米颗粒用于肿瘤中 pDNA 的控制释放。
DOI：
10.1021/bc300419g
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发表时间：
2013
影响因子：
4.7
通讯作者：
Yingyuad P
中科院分区：
文献类型：
--
作者：
Yingyuad P
在体内，纳米颗粒介导的质粒DNA(PDNA)功能递送通常需要制备表面覆盖有隐形/生物相容性聚合物(通常是聚乙二醇[PEG])的PDNA纳米颗粒。这层聚乙二醇层确保了PDNA纳米颗粒在生物体液中的胶体稳定性，并最大限度地减少了纳米颗粒与网状内皮系统的相互作用。不幸的是，一旦到达靶细胞，聚乙二醇层的存在似乎有助于降低功能递送PDNA的效率。出于这个原因，我们最近的研究重点放在“可触发”纳米粒子系统上。这些药物被设计为从给药点保持稳定，直到到达感兴趣的目标部位，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，触发治疗剂有效载荷(S)在目标部位的受控释放。在这里，我们描述了通过酶辅助纳米颗粒的触发过程来使用酶来触发pDNA介导性治疗的潜在用途的研究。我们的方法是使用具有对肿瘤局部弹性蛋白酶或基质金属蛋白酶-2消化敏感的肽基部分的PEG2000-肽基脂，并从中制备假定的酶触发的聚乙二醇化的PDNA-纳米粒。我们的结果在体外为概念提供了初步的证据。根据这些数据，我们认为这一概念应该适用于体内治疗性核酸到肿瘤细胞的功能性递送，尽管酶辅助纳米颗粒的触发机制仍有待充分表征。
Nanoparticle mediated functional delivery of plasmid DNA (pDNA) in vivo typically requires the formulation of pDNA-nanoparticles with a surface layer of stealth/biocompatibility polymer (usually poly(ethylene glycol) [PEG]). This PEG layer ensures the colloidal stability of pDNA-nanoparticles in biological fluids and minimizes nanoparticle interactions with the reticulo-endothelical system. Unfortunately, the presence of the PEG layer appears to contribute to a reduction in efficiency of functional delivery of pDNA once target cells are reached. For this reason, we have focused recent research efforts on “triggerable” nanoparticle systems. 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 potential use of enzymes to trigger pDNA-mediated therapy through a process of enzyme-assisted nanoparticle triggerability. Our approach is to use PEG2000-peptidyl lipids with peptidyl moieties sensitive to tumor-localized elastase or matrix metalloproteinase-2 digestion, and from these prepare putative enzyme-triggered PEGylated pDNA-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 tumor cells in vivo, although the mechanism for enzyme-assisted nanoparticle triggerability remains to be fully characterized.
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影响因子：
10.8
作者：
Terada, T;Iwai, M;Hashida, M
通讯作者：
Hashida, M
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作者：
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通讯作者：
Miller, Andrew D.