Cationic Shell-Cross-Linked Knedel-like (cSCK) Nanoparticles for Highly Efficient PNA Delivery

详细信息    查看全文

• 作者：Huafeng Fang^† ; ^‡ ; ; Ke Zhang^† ; ^‡ ; ^§ ; ; Gang Shen^† ; ; Karen L. Wooley*^† ; ^§ ; ; John-S
• 刊名：Molecular Pharmaceutics
• 出版年：2009
• 出版时间：April 6, 2009
• 年：2009
• 卷：6
• 期：2
• 页码：615-626
• 全文大小：505K
• 年卷期：v.6,no.2(April 6, 2009)
• ISSN：1543-8392

文摘

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) nanoparticles 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 Arg₉-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.