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 journalArticleResearchpeer-review

26 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 languageEnglish
Pages (from-to)4009-4018
Number of pages10
JournalJournal of the American Chemical Society
Volume139
Issue number11
DOIs
Publication statusPublished - 22 Mar 2017
Externally publishedYes

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