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

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Department of Polymer Science and Engineering and Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 34134, Republic of Korea
§ Department of Pharmacy, Integrated Research Institute of Pharmaceutical Sciences, and BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 14662, Republic of Korea
*E-mail: [email protected]. Phone: +82-2-2164-6533. Fax: +82-2-2164-4059.
*E-mail address: [email protected]. Phone: +82-42-821-6663. Fax: +82-42-821-8910.
Cite this: Biomacromolecules 2017, 18, 4, 1074–1085
Publication Date (Web):March 3, 2017
Copyright © 2017 American Chemical Society

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    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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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.biomac.6b01324.

    • Size data by DLS and SEM measurements; sectional images of HepG2 from confocal microscope (PDF)

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