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.
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical and Biomolecular Engineering, The University of Melbourne , Parkville, Victoria 3010, Australia.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Suma
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical and Biomolecular Engineering, The University of Melbourne , Parkville, Victoria 3010, Australia.
authors.forename: Jiwei
authors.identifier: 0000-0003-1018-4336
authors.initials: J
authors.lastname: Cui
authors.affiliation: Key Centre for Polymers and Colloids, School of Chemistry, The University of Sydney , Sydney, NSW 2006, Australia.
authors.forename: Markus
authors.initials: M
authors.lastname: Müllner
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical and Biomolecular Engineering, The University of Melbourne , Parkville, Victoria 3010, Australia.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Fu
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical and Biomolecular Engineering, The University of Melbourne , Parkville, Victoria 3010, Australia.
authors.forename: Jenny
authors.initials: J
authors.lastname: Tran
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical and Biomolecular Engineering, The University of Melbourne , Parkville, Victoria 3010, Australia.
authors.forename: Ka Fung
authors.initials: KF
authors.lastname: Noi
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical and Biomolecular Engineering, The University of Melbourne , Parkville, Victoria 3010, Australia.
authors.forename: Yi
authors.identifier: 0000-0003-0103-1207
authors.initials: Y
authors.lastname: Ju
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical and Biomolecular Engineering, The University of Melbourne , Parkville, Victoria 3010, Australia.
authors.forename: Frank
authors.identifier: 0000-0002-0197-497X
authors.initials: F
authors.lastname: Caruso
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013499:Surface Properties
chemical_list: D000903:Antibiotics, Antineoplastic; D004220:Disulfides; D010455:Peptides; D004317:Doxorubicin