Modulated Fragmentation of Proapoptotic Peptide Nanoparticles Regulates Cytotoxicity

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

doi:10.1021/jacs.6b11302

Modulated Fragmentation of Proapoptotic Peptide Nanoparticles Regulates Cytotoxicity

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

Research output: Contribution to journal › Article › Research › peer-review

40 Citations (Scopus)

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 species. In addition, a small molecule drug (i.e., doxorubicin hydrochloride) was loaded into the nanoparticles to confer synergistic cytotoxic activity, further highlighting the potential application of KLAK particles in therapeutic delivery.

Original language	English
Pages (from-to)	4009-4018
Number of pages	10
Journal	Journal of the American Chemical Society
Volume	139
Issue number	11
DOIs	https://doi.org/10.1021/jacs.6b11302
Publication status	Published - 22 Mar 2017
Externally published	Yes

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10.1021/jacs.6b11302

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ARC Centre of Excellence in Convergent Bio-Nano Science and Technology
Davis, T., Boyd, B., Bunnett, N., Porter, C., Caruso, F., Kent, S., Thordarson, P., Kearnes, M., Gooding, J., Kavallaris, M., Thurecht, K., Whittaker, A., Parton, R., Corrie, S. R., Johnston, A., McGhee, J., Greguric, I. D., Stevens, M., Lewis, J., Lee, D. S., Alexander, C., Dawson, K., Hawker, C., Haddleton, D., Thierry, B., Prestidge, C. A., Meyer, A., Jones-Jayasinghe, N., Voelcker, N. H., Nann, T. & McLean, K.
Australian Research Council (ARC), Monash University, University of Melbourne, University of New South Wales, University of Queensland , University of South Australia, Monash University – Internal Faculty Contribution, University of Wisconsin-Madison, Memorial Sloan Kettering Cancer Center, University of California System, University College Dublin, Imperial College London, University of Warwick, SungKyunKwan University, Australian Nuclear Science and Technology Organisation (ANSTO) (Australia), University of Nottingham
30/06/14 → 29/06/21
Project: Research

Cite this

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title = "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 species. In addition, a small molecule drug (i.e., doxorubicin hydrochloride) was loaded into the nanoparticles to confer synergistic cytotoxic activity, further highlighting the potential application of KLAK particles in therapeutic delivery.",

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AU - Suma, Tomoya

AU - Cui, Jiwei

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AU - Tran, Jenny

AU - Noi, Ka Fung

AU - Ju, Yi

AU - Caruso, Frank

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AB - 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 species. In addition, a small molecule drug (i.e., doxorubicin hydrochloride) was loaded into the nanoparticles to confer synergistic cytotoxic activity, further highlighting the potential application of KLAK particles in therapeutic delivery.

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Modulated Fragmentation of Proapoptotic Peptide Nanoparticles Regulates Cytotoxicity

Abstract

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Projects

ARC Centre of Excellence in Convergent Bio-Nano Science and Technology

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