Cationic Shell-Cross-Linked Knedel-like (cSCK) Nanoparticles for Highly Efficient PNA Delivery
Cationic Shell-Cross-Linked Knedel-like (cSCK) Nanoparticles for Highly Efficient PNA Delivery
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DOI：
10.1021/mp800199w
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发表时间：
2009-03-01
影响因子：
4.9
通讯作者：
Taylor, John-Stephen A.
中科院分区：
文献类型：
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作者：
Fang, Huafeng;Zhang, Ke;Taylor, John-Stephen A.
肽核酸具有许多特征，使其成为开发体外生物探针和工具的理想平台。不幸的是，它们不能通过膜限制了它们作为诊断和治疗药物在体内的应用。在本文中，我们描述了阳离子壳交联样knenel （cSCK）纳米颗粒的发展，作为PNAs进入细胞的高效载体，可以通过与PNA的静电络合。ODN杂交，或通过生物还原可切割的二硫键连接到PNA。这些传递系统比标准的脂质体/ odn介导的方法更好，也比Arg(9)介导的方法更好，在HeLa细胞中传递PNA，具有更低的毒性和更高的生物活性。cSCKs也被发现促进PNAs的内吞作用和内体释放，而它们自己仍然被困在内体中。
Peptide nucleic acids have a number of features that make them an ideal platform for the development of in vitro biological probes and tools. Unfortunately, their inability to pass through membranes has limited their in vivo application as diagnostic and therapeutic agents. Herein, we describe the development of cationic shell-cross-linked knedel-like (cSCK) nano-particles as highly efficient vehicles for the delivery of PNAs into cells, either through electrostatic complexation with a PNA.ODN hybrid, or through a bioreductively cleavable disulfide linkage to a PNA. These delivery systems are better than the standard Lipofectamine/ODN-mediated method and much better than the Arg(9)-mediated method for PNA delivery in HeLa cells, showing lower toxicity and higher bioactivity. The cSCKs were also found to facilitate both endocytosis and endosomal release of the PNAs, while themselves remaining trapped in the endosomes.