Selecting improved peptidyl motifs for cytosolic delivery of disparate protein and nanoparticle materials.
Selecting improved peptidyl motifs for cytosolic delivery of disparate protein and nanoparticle materials.
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DOI：
10.1021/nn400702r
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发表时间：
2013-05-28
期刊：
影响因子：
17.1
通讯作者：
Medintz, Igor L.
中科院分区：
文献类型：
--
作者：
Boeneman, Kelly;Delehanty, James B.;Blanco-Canosa, Juan B.;Susumu, Kimihiro;Stewart, Michael H.;Oh, Eunkeu;Huston, Alan L.;Dawson, Glyn;Ingale, Sampat;Walters, Ryan;Domowicz, Miriam;Deschamps, Jeffrey R.;Algar, W. Russ;DiMaggio, Stassi;Manono, Janet;Spillmann, Christopher M.;Thompson, Darren;Jennings, Travis L.;Dawson, Philip E.;Medintz, Igor L.
关键词：
细胞穿透肽促进从小的造影剂到较大的蛋白质和纳米颗粒的各种材料的有效细胞内摄取。然而，一个重大的障碍仍然是在随后的区室化/内体封存的大多数这些货物。先前的功能筛选表明，最初设计用于向神经元递送棕榈酰蛋白硫酯酶抑制剂的模块肽可以介导培养细胞中的内体逃逸。在这里，我们详细介绍了这种肽介导量子点（QD）的胞质传递到广泛的细胞类型，脑组织培养和发育中的鸡胚在一个显着的无毒方式的能力相关的属性。该肽进一步促进了大蛋白质、树枝状聚合物和其他纳米颗粒材料的有效内体逃逸。我们进行了一个迭代的结构-活性关系分析的肽离散修改的关键组件，包括长度，电荷，脂肪酸含量和它们的顺序，使用比较，半定量测定。这种方法使我们能够定义内体逃逸所需的关键基序，选择更有效的逃逸序列，沿着意外地鉴定出由一个亚甲基修饰的序列，该序列特异性地将QD靶向细胞膜。我们解释我们的结果在一个模型中的肽功能和突出的影响，在体内标记和纳米颗粒介导的药物递送，通过使用不同的肽共同提供货物到细胞和从事多功能标记。
Cell penetrating peptides facilitate efficient intracellular uptake of diverse materials ranging from small contrast agents to larger proteins and nanoparticles. However, a significant impediment remains in the subsequent compartmentalization/endosomal sequestration of most of these cargoes. Previous functional screening suggested that a modular peptide originally designed to deliver palmitoyl-protein thioesterase inhibitors to neurons could mediate endosomal escape in cultured cells. Here, we detail properties relevant to this peptide’s ability to mediate cytosolic delivery of quantum dots (QDs) to a wide range of cell-types, brain tissue culture and a developing chick embryo in a remarkably non-toxic manner. The peptide further facilitated efficient endosomal escape of large proteins, dendrimers and other nanoparticle materials. We undertook an iterative structure-activity relationship analysis of the peptide by discretely modifying key components including length, charge, fatty acid content and their order using a comparative, semi-quantitative assay. This approach allowed us to define the key motifs required for endosomal escape, to select more efficient escape sequences, along with unexpectedly identifying a sequence modified by one methylene group that specifically targeted QDs to cellular membranes. We interpret our results within a model of peptide function and highlight implications for in vivo labeling and nanoparticle-mediated drug delivery by using different peptides to co-deliver cargoes to cells and engage in multifunctional labeling.
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DOI：
10.1034/j.1399-3011.2002.201005.x
发表时间：
2002-08-01
期刊：
JOURNAL OF PEPTIDE RESEARCH
影响因子：
--
作者：
Banerjee, R;Basu, G;Roy, S
通讯作者：
Roy, S
影响因子：
15
作者：
Algar, W. Russ;Wegner, David;Medintz, Igor L.
通讯作者：
Medintz, Igor L.
影响因子：
2.5
作者：
Delehanty, James B.;Bradburne, Christopher E.;Medintz, Igor L.
通讯作者：
Medintz, Igor L.
影响因子：
21.8
作者：
Mager, Morgan D.;LaPointe, Vanessa;Stevens, Molly M.
通讯作者：
Stevens, Molly M.
影响因子：
4.7
作者：
Kobayashi, Sachiko;Nakase, Ikuhiko;Futaki, Shiroh
通讯作者：
Futaki, Shiroh