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)2conjugate) 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)2self-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)2NPs 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)2NPs can induce fast drug release with enhanced mitochondrial uptake and have a better therapeutic effect than nonbioreducible NPs.
authors.forename: Zehedina
authors.initials: Z
authors.lastname: Khatun
authors.affiliation: 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.
authors.forename: Yeon Su
authors.initials: YS
authors.lastname: Choi
authors.forename: Yu Gyeong
authors.initials: YG
authors.lastname: Kim
authors.forename: Kwonhyeok
authors.initials: K
authors.lastname: Yoon
authors.forename: Md
authors.initials: M
authors.lastname: Nurunnabi
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Eunji
authors.identifier: 0000-0001-7494-1776
authors.initials: E
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Han Chang
authors.identifier: 0000-0003-0696-1155
authors.initials: HC
authors.lastname: Kang
authors.forename: Kang Moo
authors.identifier: 0000-0002-2406-6659
authors.initials: KM
authors.lastname: Huh
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D056945:Hep G2 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008928:Mitochondria / Q000187:drug effects*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011092:Polyethylene Glycols; D004317:Doxorubicin