Cationic shell-cross-linked knedel-Like (cSCK) nanoparticles for highly efficient PNA delivery

Huafeng Fang, Ke Zhang, Gang Shen, Karen L. Wooley, John Stephen A. Taylor

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


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.

Original languageEnglish
Pages (from-to)615-626
Number of pages12
JournalMolecular Pharmaceutics
Issue number2
StatePublished - Apr 6 2009


  • Bioreductively cleavable linker
  • Cationic
  • Cell penetrating
  • Endosome
  • Endosome disruption
  • Nanoparticle
  • PNA
  • Shell-cross-linked
  • Splice correction
  • Transfection


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