Enzyme-triggered PEGylated pDNA-nanoparticles for controlled release of pDNA in tumors
| Autor: | Mathieu Mével, Maya Thanou, Stefan Furegati, Peerada Yingyuad, Christos Kontogiorgis, Carla Prata, Andrew D. Miller |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Biocompatibility
Biomedical Engineering Pharmaceutical Science Nanoparticle Bioengineering Nanotechnology Polyethylene Glycols chemistry.chemical_compound In vivo Neoplasms PEG ratio Humans Pharmacology chemistry.chemical_classification Organic Chemistry Gene Transfer Techniques Polymer DNA Controlled release Enzyme chemistry Delayed-Action Preparations Biophysics MCF-7 Cells Nanoparticles Ethylene glycol Biotechnology |
| Zdroj: | Bioconjugate chemistry. 24(3) |
| ISSN: | 1520-4812 |
| Popis: | Nanoparticle mediated functional delivery of plasmid DNA (pDNA) in vivo typically requires the formulation of pDNA-nanoparticles with a surface layer of stealth/biocompatibility polymer (usually poly(ethylene glycol) [PEG]). This PEG layer ensures the colloidal stability of pDNA-nanoparticles in biological fluids and minimizes nanoparticle interactions with the reticulo-endothelical system. Unfortunately, the presence of the PEG layer appears to contribute to a reduction in efficiency of functional delivery of pDNA once target cells are reached. For this reason, we have focused recent research efforts on "triggerable" nanoparticle systems. These are designed to be stable from the point of administration until a target site of interest is reached, then triggered for the controlled release of therapeutic agent payload(s) at the target site by changes in local endogenous conditions or through the application of some exogenous stimulus. Here, we describe investigations into the potential use of enzymes to trigger pDNA-mediated therapy through a process of enzyme-assisted nanoparticle triggerability. Our approach is to use PEG(2000)-peptidyl lipids with peptidyl moieties sensitive to tumor-localized elastase or matrix metalloproteinase-2 digestion, and from these prepare putative enzyme-triggered PEGylated pDNA-nanoparticles. Our results provide initial proof of concept in vitro. From these data, we propose that this concept should be applicable for functional delivery of therapeutic nucleic acids to tumor cells in vivo, although the mechanism for enzyme-assisted nanoparticle triggerability remains to be fully characterized. |
| Databáze: | OpenAIRE |
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