Modulated Fragmentation of Proapoptotic Peptide Nanoparticles Regulates Cytotoxicity

Abstract

Peptides perform a diverse range of physiologically important functions. The formulation of nanoparticles directly from functional peptides would therefore offer a versatile and robust platform to produce highly functional therapeutics. Herein, we engineered proapoptotic peptide nanoparticles from mitochondria-disrupting KLAK peptides using a template-assisted approach. The nanoparticles were designed to disassemble into free native peptides via the traceless cleavage of disulfide-based cross-linkers. Furthermore, the cytotoxicity of the nanoparticles was tuned by controlling the kinetics of disulfide bond cleavage, and the rate of regeneration of the native peptide from the precursor specie..