Intracellular delivery of peptide drugs using viral nanoparticles of bacteriophage P22: covalent loading and cleavable release.

ABSTRACT

Peptides have great potential in the treatment of various diseases because of their high specificity and safety. However, their application has been limited by the lack of appropriate delivery techniques. In this study, we have demonstrated the intracellular delivery of peptides using viral nanoparticles (VNPs) of bacteriophage P22 through covalent loading of two different peptides with synergistic cytotoxic effects and controllable release triggered by Cathepsin B, a highly over-expressed protease in many tumors. Fluorescence imaging of the intracellular localization of the P22 VNPs and the peptides evidenced that the delivery system could be transported as designed. Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis revealed the cytotoxic effects of the peptides on MDA-MB-231 tumor cells. These results have confirmed the feasibility of genetically fusing cargo peptides to the capsid protein of P22 and cleavable release thereafter. This study may be instructive for the design of drug delivery systems and multifunctional theranostic devices based on P22 VNPs.