Cationic shell-cross-linked knedel-like (cSCK) nanoparticles for highly efficient PNA delivery.
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 Arg(g)-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.
Fang
Huafeng
H
Department of Chemistry, Washington University, One Brookings Drive, St. Louis, Missouri 63130, USA.
Zhang
Ke
K
Shen
Gang
G
Wooley
Karen L
KL
Taylor
John-Stephen A
JS
D002412:Cations / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D004705:Endocytosis; D011992:Endosomes; D006367:HeLa Cells; D006801:Humans; D008055:Lipids; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D053758:Nanoparticles; D009841:Oligonucleotides / Q000008:administration & dosage*; D020135:Peptide Nucleic Acids / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D002412:Cations; D008055:Lipids; C086724:Lipofectamine; D009841:Oligonucleotides; D020135:Peptide Nucleic Acids; D012333:RNA, Messenger; D008156:Luciferases