Journal
JOURNAL OF CONTROLLED RELEASE
Volume 205, Issue -, Pages 15-24Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2014.11.012
Keywords
PVA nanogel; Inverse nanoprecipitation; Charge-conversion; Stimuli-responsive; Drug delivery
Funding
- German Research Foundation [SFB 1112]
- Alexander von Humboldt Foundation
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Charge-conversional and reduction-sensitive polyvinyl alcohol (PVA) nanogels were developed for efficient cancer treatment by enhanced cell uptake and intracellular triggered doxorubicin (DOX) release. These PVA nanogels were prepared in a straightforward manner by inverse nanoprecipitation via click reaction with an average diameter of 118 nm. The introduction of COOH into the PVA nanogels efficiently improved the DOX encapsulation due to the electrostatic interaction. The in vitro release result showed that the decrease of electrostatic interaction between COOH and DOX under a mimicking endosomal pH, in combination with the cleavage of the intervening disulfide bonds in response to a high glutathione (GSH) concentration led to a fast and complete release of DOX. Furthermore, confocal laser scanning microscopy (CLSM) revealed that the ultra pH-sensitive terminal groups allowed nanogels to reverse their surface charge from negative to positive under a tumor extracellular pH (6.5-6.8) which facilitated cell internalization. MTT assays and real time cell analysis (RTCA) showed that these DOX-loaded charge-conversional and reducible PVA nanogels had much better cell toxicity than DOX-loaded non-charge-conversional or reduction-insensitive PVA nanogels following 48 h of incubation. These novel charge-conversional and stimuli-responsive PVA nanogels are highly promising for targeted intracellular anticancer drug release. (C) 2014 Elsevier B.V. All rights reserved.
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