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Encapsulation of oligonucleotides in stealth Me.PEG-PLA50 nanoparticles by complexation with structured oligopeptides
C Emile1, D Bazile2, F Herman2
1a Muséum National d'Histoire Naturelle, Laboratoire de Biophysique, Paris, France.
Drug Delivery
|January 22, 2016
Summary
Oligopeptides with specific amino acid sequences bind strongly to oligonucleotides, forming complexes that can be encapsulated in nanoparticles for potential drug delivery applications.
Area of Science:
- Biochemistry
- Materials Science
- Nanotechnology
Background:
- Oligopeptides are short chains of amino acids.
- Oligonucleotides are short DNA or RNA molecules.
- Nanoparticles are tiny particles used in drug delivery.
Purpose of the Study:
- To investigate the binding affinity of different oligopeptides to oligonucleotides.
- To explore the relationship between oligopeptide secondary structure and binding affinity.
- To develop a method for encapsulating oligonucleotide/oligopeptide complexes in nanoparticles.
Main Methods:
- Synthesized oligopeptides with alternating hydrophilic-hydrophobic amino acids.
- Assessed binding affinity between oligopeptides and a 13-mer oligonucleotide.
- Determined oligopeptide secondary structures (alpha-helix, beta-sheet) upon complexation.
- Encapsulated non-water-soluble complexes in Me.PEG-PLA50 nanoparticles via coprecipitation.
Main Results:
- Oligopeptides H-(leu-lys-lys-leu)10-OH and H-(leu-lys-leu-lys)10-OH showed higher affinity for the oligonucleotide compared to a control.
- Increased binding affinity correlated with specific secondary structures (alpha-helix and beta-sheet).
- Tight ion-pairing between oligonucleotide phosphates and oligopeptide lysines facilitated complex formation.
- Resulting oligonucleotide/oligopeptide complexes were successfully encapsulated in Me.PEG-PLA50 nanoparticles.
Conclusions:
- The secondary structure of oligopeptides significantly influences their binding affinity to oligonucleotides.
- Specific oligopeptide-oligonucleotide interactions enable the formation of non-water-soluble complexes.
- Coprecipitation with Me.PEG-PLA50 is an effective method for nanoparticle encapsulation of these complexes, paving the way for novel delivery systems.
