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 | |
| State | Published - 10 Apr 2017 |
Bibliographical note
Funding Information:This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF-2015R1D1A1A09056741) funded by the Ministry of Education, Science and Technology and the Industrial Technology Innovation Program (10060059, Externally Actuatable Nanorobot System for Precise Targeting and Controlled Releasing of Drugs) funded by the Ministry of Trade, Industry and Energy (MOTIE, Korea).
Publisher Copyright:
© 2017 American Chemical Society.