Bioreducible Poly(ethylene glycol)-Triphenylphosphonium Conjugate as a Bioactivable Mitochondria-Targeting Nanocarrier

Zehedina Khatun; Yu Gyeong Kim; Kwonhyeok Yoon; Md Nurunnabi; Li Li; Kang Moo Huh; Eunji Lee; Han Chang Kang

doi:10.1021/acs.biomac.6b01324

Bioreducible Poly(ethylene glycol)-Triphenylphosphonium Conjugate as a Bioactivable Mitochondria-Targeting Nanocarrier

Zehedina Khatun
, Yu Gyeong Kim
, Kwonhyeok Yoon
, Md Nurunnabi
, Li Li
, Kang Moo Huh
, Eunji Lee
, Han Chang Kang

Chungnam National University
The Catholic University of Korea

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

43 Scopus citations

Abstract

Bioactivable nanocarrier systems have favorable characteristics such as high cellular uptake, target specificity, and an efficient intracellular release mechanism. In this study, we developed a bioreducible methoxy polyethylene glycol (mPEG)-triphenylphosphonium (TPP) conjugate (i.e., mPEG-(ss-TPP)₂ conjugate) as a vehicle for mitochondrial drug delivery. A bioreducible linkage with two disulfide bond-containing end groups was used at one end of the hydrophilic mPEG for conjugation with lipophilic TPP molecules. The amphiphilic mPEG-(ss-TPP)₂ self-assembled in aqueous media, which thereby formed core-shell structured nanoparticles (NPs) with good colloidal stability, and efficiently encapsulated the lipophilic anticancer drug doxorubicin (DOX). The DOX-loaded mPEG-(ss-TPP)₂ NPs were characterized in terms of their physicochemical and morphological properties, drug-loading and release behaviors, in vitro anticancer effects, and mitochondria-targeting capacity. Our results suggest that bioreducible DOX-loaded mPEG-(ss-TPP)₂ NPs can induce fast drug release with enhanced mitochondrial uptake and have a better therapeutic effect than nonbioreducible NPs.

Original language	English
Pages (from-to)	1074-1085
Number of pages	12
Journal	Biomacromolecules
Volume	18
Issue number	4
DOIs	https://doi.org/10.1021/acs.biomac.6b01324
State	Published - 10 Apr 2017

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© 2017 American Chemical Society.

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title = "Bioreducible Poly(ethylene glycol)-Triphenylphosphonium Conjugate as a Bioactivable Mitochondria-Targeting Nanocarrier",

abstract = "Bioactivable nanocarrier systems have favorable characteristics such as high cellular uptake, target specificity, and an efficient intracellular release mechanism. In this study, we developed a bioreducible methoxy polyethylene glycol (mPEG)-triphenylphosphonium (TPP) conjugate (i.e., mPEG-(ss-TPP)2 conjugate) as a vehicle for mitochondrial drug delivery. A bioreducible linkage with two disulfide bond-containing end groups was used at one end of the hydrophilic mPEG for conjugation with lipophilic TPP molecules. The amphiphilic mPEG-(ss-TPP)2 self-assembled in aqueous media, which thereby formed core-shell structured nanoparticles (NPs) with good colloidal stability, and efficiently encapsulated the lipophilic anticancer drug doxorubicin (DOX). The DOX-loaded mPEG-(ss-TPP)2 NPs were characterized in terms of their physicochemical and morphological properties, drug-loading and release behaviors, in vitro anticancer effects, and mitochondria-targeting capacity. Our results suggest that bioreducible DOX-loaded mPEG-(ss-TPP)2 NPs can induce fast drug release with enhanced mitochondrial uptake and have a better therapeutic effect than nonbioreducible NPs.",

author = "Zehedina Khatun and Kim, \{Yu Gyeong\} and Kwonhyeok Yoon and Md Nurunnabi and Li Li and Huh, \{Kang Moo\} and Eunji Lee and Kang, \{Han Chang\}",

note = "Publisher Copyright: {\textcopyright} 2017 American Chemical Society.",

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doi = "10.1021/acs.biomac.6b01324",

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AU - Khatun, Zehedina

AU - Kim, Yu Gyeong

AU - Yoon, Kwonhyeok

AU - Nurunnabi, Md

AU - Li, Li

AU - Huh, Kang Moo

AU - Lee, Eunji

AU - Kang, Han Chang

PY - 2017/4/10

Y1 - 2017/4/10

N2 - Bioactivable nanocarrier systems have favorable characteristics such as high cellular uptake, target specificity, and an efficient intracellular release mechanism. In this study, we developed a bioreducible methoxy polyethylene glycol (mPEG)-triphenylphosphonium (TPP) conjugate (i.e., mPEG-(ss-TPP)2 conjugate) as a vehicle for mitochondrial drug delivery. A bioreducible linkage with two disulfide bond-containing end groups was used at one end of the hydrophilic mPEG for conjugation with lipophilic TPP molecules. The amphiphilic mPEG-(ss-TPP)2 self-assembled in aqueous media, which thereby formed core-shell structured nanoparticles (NPs) with good colloidal stability, and efficiently encapsulated the lipophilic anticancer drug doxorubicin (DOX). The DOX-loaded mPEG-(ss-TPP)2 NPs were characterized in terms of their physicochemical and morphological properties, drug-loading and release behaviors, in vitro anticancer effects, and mitochondria-targeting capacity. Our results suggest that bioreducible DOX-loaded mPEG-(ss-TPP)2 NPs can induce fast drug release with enhanced mitochondrial uptake and have a better therapeutic effect than nonbioreducible NPs.

AB - Bioactivable nanocarrier systems have favorable characteristics such as high cellular uptake, target specificity, and an efficient intracellular release mechanism. In this study, we developed a bioreducible methoxy polyethylene glycol (mPEG)-triphenylphosphonium (TPP) conjugate (i.e., mPEG-(ss-TPP)2 conjugate) as a vehicle for mitochondrial drug delivery. A bioreducible linkage with two disulfide bond-containing end groups was used at one end of the hydrophilic mPEG for conjugation with lipophilic TPP molecules. The amphiphilic mPEG-(ss-TPP)2 self-assembled in aqueous media, which thereby formed core-shell structured nanoparticles (NPs) with good colloidal stability, and efficiently encapsulated the lipophilic anticancer drug doxorubicin (DOX). The DOX-loaded mPEG-(ss-TPP)2 NPs were characterized in terms of their physicochemical and morphological properties, drug-loading and release behaviors, in vitro anticancer effects, and mitochondria-targeting capacity. Our results suggest that bioreducible DOX-loaded mPEG-(ss-TPP)2 NPs can induce fast drug release with enhanced mitochondrial uptake and have a better therapeutic effect than nonbioreducible NPs.

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ER -

Bioreducible Poly(ethylene glycol)-Triphenylphosphonium Conjugate as a Bioactivable Mitochondria-Targeting Nanocarrier

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