Non-natural Amino Acids Containing Peptide-Capped Gold Nanoparticles for Drug Delivery Application

Peptide-based capping agents for gold nanoparticles (GNPs) are possible alternatives for capping and derivatizing GNPs, but suffer from a major disadvantage of sensitivity toward non specific proteases, which may limit their in vivo utility. Using non-natural analogs of natural α-amino acids offer an attractive alternate strategy to circumvent this potential bottleneck in realizing full potential of peptide based capping gents for GNPs for biological applications. Here, we have designed and developed pentapeptides containing non-natural amino acid (α,β-dehydrophenylalanine and α-aminoisobutyric acid) as capping agents for GNPs. All these peptides were able to efficiently cap GNPs and peptide induced aggregation was not observed. Peptide capped GNPs showed minimal cytotoxicity to mammalian cell lines (HeLa and L929) as well as mice spleenocytes. They encapsulated small drug like molecules and peptide capped GNPs entrapping drugs were more efficient in killing HeLa cells compared to the free drug. Therefore, these non-natural amino acid containing peptide-capped GNPs may be further developed as alternate drug delivery vehicles.