One of the major weaknesses of therapeutic peptides is their sensitivity to degradation by proteolytic enzymes in vivo. Gold nanoparticles (GNPs) are a good carrier for therapeutic peptides to improve their stability and cellular uptake in vitro and in vivo. We conjugated the anticancer KT2 peptide as an anticancer peptide model to PEGylated GNPs (GNPs-PEG) and investigated the peptide stability, cellular uptake and ability of the GNPs-KT2-PEG conjugates to induce MDA-MB-231 human breast cancer cell death. We found that 11 nm GNPs protected the conjugated KT2 peptide from trypsin proteolysis, keeping it stable up to 0.128% trypsin, which is higher than the serum trypsin concentration (range 0.0000285 ± 0.0000125%) reported by Lake-Bakaar, G. et al., 1979. GNPs significantly enhanced the cellular uptake of KT2 peptides after conjugation. Free KT2 peptides pretreated with trypsin were not able to kill MDA-MB-231 cells due to proteolysis, while GNPs-KT2-PEG was still able to exert effective cancer cell killing after trypsin treatment at levels comparable to GNPs-KT2-PEG without enzyme pretreatment. The outcome of this study highlights the utility of conjugated anticancer peptides on nanoparticles to improve peptide stability and retain anticancer ability.
This journal is © The Royal Society of Chemistry.