Abstract
Nucleic acid (NA) based drugs offer the potential of highly selective treatments for malignant diseases. They act as an initially inactive pro-drug being activated at the intended site of action, either by translation into a protein in case of plasmid DNA or through expression shutdown by interfering specifically with messenger RNA (RNAi technology). In case of already metastasized cancer, systemic treatment via the blood stream is often inevitable to reach the lesion. This makes it necessary to protect NAs from enzymatic degradation, but also to target them to the tumor with appropriate ligands. Polycationic molecules can provide such functions by condensing NAs into virus sized particles by virtue of charge interaction with the negatively charged phosphate backbone of NAs. Here we review the application of NA carrier systems based on the polycation polyethylenimine (PEI), where peptide based ligands are attached to the polycation via heterobifunctional polyethylene glycol linker molecules. Conjugate synthesis, in vitro testing and in vivo application in subcutaneous and disseminated cancer models in rodents are discussed.
Keywords: Biodegradable, cancer gene therapy, epidermal growth factor receptor, gene delivery, imaging, PEG, polyethylenimine, polyplex, targeting, tumor necrosis factor alpha.
Current Medicinal Chemistry
Title:Nucleic Acid Carrier Systems Based on Polyethylenimine Conjugates for the Treatment of Metastatic Tumors
Volume: 20 Issue: 28
Author(s): David Schaffert and Manfred Ogris
Affiliation:
Keywords: Biodegradable, cancer gene therapy, epidermal growth factor receptor, gene delivery, imaging, PEG, polyethylenimine, polyplex, targeting, tumor necrosis factor alpha.
Abstract: Nucleic acid (NA) based drugs offer the potential of highly selective treatments for malignant diseases. They act as an initially inactive pro-drug being activated at the intended site of action, either by translation into a protein in case of plasmid DNA or through expression shutdown by interfering specifically with messenger RNA (RNAi technology). In case of already metastasized cancer, systemic treatment via the blood stream is often inevitable to reach the lesion. This makes it necessary to protect NAs from enzymatic degradation, but also to target them to the tumor with appropriate ligands. Polycationic molecules can provide such functions by condensing NAs into virus sized particles by virtue of charge interaction with the negatively charged phosphate backbone of NAs. Here we review the application of NA carrier systems based on the polycation polyethylenimine (PEI), where peptide based ligands are attached to the polycation via heterobifunctional polyethylene glycol linker molecules. Conjugate synthesis, in vitro testing and in vivo application in subcutaneous and disseminated cancer models in rodents are discussed.
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Cite this article as:
Schaffert David and Ogris Manfred, Nucleic Acid Carrier Systems Based on Polyethylenimine Conjugates for the Treatment of Metastatic Tumors, Current Medicinal Chemistry 2013; 20 (28) . https://dx.doi.org/10.2174/0929867311320280004
DOI https://dx.doi.org/10.2174/0929867311320280004 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
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