Delivery of small interfering RNA by peptide-targeted mesoporous silica nanoparticle-supported lipid bilayers.
Delivery of small interfering RNA by peptide-targeted mesoporous silica nanoparticle-supported lipid bilayers.
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DOI：
10.1021/nn204102q
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发表时间：
2012-03-27
期刊：
影响因子：
17.1
通讯作者：
Brinker CJ
中科院分区：
文献类型：
--
作者：
Ashley CE;Carnes EC;Epler KE;Padilla DP;Phillips GK;Castillo RE;Wilkinson DC;Wilkinson BS;Burgard CA;Kalinich RM;Townson JL;Chackerian B;Willman CL;Peabody DS;Wharton W;Brinker CJ
小干扰rna （siRNA）的治疗潜力受到递送平台的严重限制，这些平台可以保护siRNA免受降解，以高特异性和高效率将其递送到靶细胞，并促进其内体逃逸和细胞质分散。在这里，我们报告了介孔二氧化硅纳米颗粒支持的脂质双层（或“原始细胞”），表现出多种特性，克服了现有递送平台的许多限制。原始细胞具有比相应的脂质纳米颗粒大10到100倍的siRNA容量，并且在生理条件下孵育时显着更加稳定。携带sirna混合物的原始细胞以一种依赖于适当靶向肽存在的方式与细胞结合，并通过内吞途径随后的内体破坏，促进沉默核苷酸向细胞质的传递。sirna靶向的每个基因的表达在蛋白质水平上被抑制，导致生长停滞和细胞凋亡的有效诱导。将缺乏靶向肽识别抗原表达的对照细胞与装载sirna的原细胞孵育，既不会导致蛋白表达的抑制，也不会导致细胞凋亡，这表明细胞毒性活性具有精确的特异性。就装载能力、靶向能力和作用效力而言，原始细胞作为治疗性寡核苷酸的递送平台提供了独特的属性。
The therapeutic potential of small interfering RNAs (siRNAs) is severely limited by the availability of delivery platforms that protect siRNA from degradation, deliver it to the target cell with high specificity and efficiency, and promote its endosomal escape and cytosolic dispersion. Here we report that mesoporous silica nanoparticle-supported lipid bilayers (or ‘protocells’), exhibit multiple properties that overcome many of the limitations of existing delivery platforms. Protocells have a 10- to 100-fold greater capacity for siRNA than corresponding lipid nanoparticles and are markedly more stable when incubated under physiological conditions. Protocells loaded with a cocktail of siRNAs bind to cells in a manner dependent on the presence of an appropriate targeting peptide and, through an endocytic pathway followed by endosomal disruption, promote delivery of the silencing nucleotides to the cytoplasm. The expression of each of the genes targeted by the siRNAs was shown to be repressed at the protein level, resulting in a potent induction of growth arrest and apoptosis. Incubation of control cells that lack expression of the antigen recognized by the targeting peptide with siRNA-loaded protocells induced neither repression of protein expression nor apoptosis, indicating the precise specificity of cytotoxic activity. In terms of loading capacity, targeting capabilities, and potency of action, protocells provide unique attributes as a delivery platform for therapeutic oligonucleotides.
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影响因子：
46.9
作者：
Judge, AD;Sood, V;MacLachlan, I
通讯作者：
MacLachlan, I
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作者：
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