Journal article

Modulated Fragmentation of Proapoptotic Peptide Nanoparticles Regulates Cytotoxicity

Tomoya Suma, Jiwei Cui, Markus Muellner, Shiwei Fu, Jenny Tran, Ka Fung Noi, Yi Ju, Frank Caruso

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | AMER CHEMICAL SOC | Published : 2017

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..

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Grants

Awarded by Australian Research Council (ARC) Centre of Excellence in Convergent Bio-Nano Science and Technology


Awarded by ARC under the Australian Laureate Fellowship


Funding Acknowledgements

This research was conducted and funded by the Australian Research Council (ARC) Centre of Excellence in Convergent Bio-Nano Science and Technology (Project CE140100036) and the ARC under the Australian Laureate Fellowship (F.C., FL120100030) scheme. This work was performed in part at the Materials Characterisation and Fabrication Platform (MCFP) at the University of Melbourne and the Victorian Node of the Australian National Fabrication Facility (ANFF).