Example 20
Coupling of the ligand to the nanoparticle may be achieved uniquely by following an inclusion compound protocol with β-cyclodextrin (β-CD) on the particle spontaneously interacting with adamantane on the peptide or small molecule ligand to form an inclusion complex. Briefly, cyclodextrin-PEG-DSPE derivative will be synthesized via mono-6-deoxy-6-amino-β-cyclodextrin. One of the seven primary hydroxyl groups of β-cyclodextrin will be tosylated using p-toluenesulfonyl chloride. Substitution of the tosyl group by azide and subsequent reduction with triphenylphosphine will yield mono-6-deoxy-6-amino-β-cyclodextrin. Carboxyl-activated PEG-DSPE will be conjugated to mono-6-deoxy-6-amino-β-cyclodextrin to produce cyclodextrin-PEG-DSPE. Adamantane-amine will be directly conjugated through a short spacer in the solid phase peptide synthesis to the carboxyl end of the peptide to produce adamantane-peptide/ligand. The simple room temperature mixing of adamantane-amine and β-cyclodextrin bearing nanoparticle will produce peptide coupled targeted nanoparticle.
