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 | |
| Publication status | Published - 22 Mar 2017 |
| Externally published | Yes |
Cite this
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Modulated Fragmentation of Proapoptotic Peptide Nanoparticles Regulates Cytotoxicity. / Suma, Tomoya; Cui, Jiwei; Müllner, Markus; Fu, Shiwei; Tran, Jenny; Noi, Ka Fung; Ju, Yi; Caruso, Frank.
In: Journal of the American Chemical Society, Vol. 139, No. 11, 22.03.2017, p. 4009-4018.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Modulated Fragmentation of Proapoptotic Peptide Nanoparticles Regulates Cytotoxicity
AU - Suma, Tomoya
AU - Cui, Jiwei
AU - Müllner, Markus
AU - Fu, Shiwei
AU - Tran, Jenny
AU - Noi, Ka Fung
AU - Ju, Yi
AU - Caruso, Frank
PY - 2017/3/22
Y1 - 2017/3/22
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85016155685&partnerID=8YFLogxK
U2 - 10.1021/jacs.6b11302
DO - 10.1021/jacs.6b11302
M3 - Article
VL - 139
SP - 4009
EP - 4018
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 11
ER -