Document Detail


Effects of cell-penetrating peptides and pegylation on transfection efficiency of polyethylenimine in mouse lungs.
MedLine Citation:
PMID:  18780309     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Cell-penetrating peptides (CPPs) could potentially be used as vectors for intracellular delivery of proteins, peptides and nucleic acids. The present study examined different CPPs, such as TAT-derived and arginine rich sequences, as well as model amphiphilic peptide, with respect to transfection efficiency of pegylated polyethylenimine (PEI) in A549, Calu-3 cells and in mice after intra-tracheal administration. METHODS: The conjugates were prepared by the coupling of CPPs to PEI via a heterobifunctional polyethylene glycol (PEG) linker, resulting in the bioconjugates CPP-PEG-PEI. Structures were successfully confirmed by (1)H-nuclear magnetic resonance and diffusion-ordered spectroscopy. Unmodified PEI 25 kDa was compared with pegylated PEI, and aggregation tendency in cell culture medium, interaction with mucin and stability against heparin was assayed. After evaluating transfection efficiency of the polymers in two different lung cell lines, luciferase reporter gene expression was determined in mouse lungs. RESULTS: All conjugates showed superior transfection efficiency compared to unmodified PEI 25 kDa. The conjugates sizes were generally < 300 nm, thus enabling them to penetrate through the mucus lining of the lung and reach the target cells. Coupling of CPPs to PEG-PEI, however, did not significantly improve transfection efficiency in A549 cells, calu-3 cells and in mouse lungs. CONCLUSIONS: We show that small and stable polyplex size achieved by pegylation is favourable for successful pulmonary gene delivery. Compared to PEI 25 kDa, pegylated PEI and CPP-PEG-PEI displayed enhanced transfection efficiency both in vitro and in vivo.
Authors:
Juliane Nguyen; Xiulan Xie; Michael Neu; Rio Dumitrascu; Regina Reul; Johannes Sitterberg; Udo Bakowsky; Ralph Schermuly; Ludger Fink; Thomas Schmehl; Tobias Gessler; Werner Seeger; Thomas Kissel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The journal of gene medicine     Volume:  10     ISSN:  1521-2254     ISO Abbreviation:  J Gene Med     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-05     Completed Date:  2008-12-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815764     Medline TA:  J Gene Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  1236-46     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutics and Biopharmacy, Philipps Universität, Marburg, Germany.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Cells, Cultured
Gene Transfer Techniques
Genetic Vectors / administration & dosage
Lung / metabolism*
Magnetic Resonance Spectroscopy
Mice
Microscopy, Atomic Force
Molecular Sequence Data
Peptides / administration & dosage,  chemistry*
Polyethylene Glycols / chemistry*
Polyethyleneimine / administration & dosage,  chemistry*
Transfection*
Chemical
Reg. No./Substance:
0/Peptides; 0/Polyethylene Glycols; 9002-98-6/Polyethyleneimine

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