Hypoxia-responsive polymeric nanoparticles for tumor-targeted drug delivery

Authors
Thambi, ThavasyappanDeepagan, V. G.Yoon, Hong YeolHan, Hwa SeungKim, Seol-HeeSon, SoyoungJo, Dong-GyuAhn, Cheol-HeeSuh, Yung DougKim, KwangmeyungKwon, Ick ChanLee, Doo SungPark, Jae Hyung
Issue Date
2014-02
Publisher
ELSEVIER SCI LTD
Citation
BIOMATERIALS, v.35, no.5, pp.1735 - 1743
Abstract
Hypoxia is a condition found in various intractable diseases. Here, we report self-assembled nanoparticles which can selectively release the hydrophobic agents under hypoxic conditions. For the preparation of hypoxia-responsive nanoparticles (HR-NPs), a hydrophobically modified 2-nitroimidazole derivative was conjugated to the backbone of the carboxymethyl dextran (CM-Dex). Doxorubicin (DOX), a model drug, was effectively encapsulated into the HR-NPs. The HR-NPs released DOX in a sustained manner under the normoxic condition (physiological condition), whereas the drug release rate. remarkably increased under the hypoxic condition. From in vitro cytotoxicity tests, it was found the DOX-loaded HR-NPs showed higher toxicity to hypoxic cells than to normoxic cells. Microscopic observation showed that the HR-NPs could effectively deliver DOX into SCC7 cells under hypoxic conditions. In vivo biodistribution study demonstrated that HR-NPs were selectively accumulated at the hypoxic tumor tissues. As consequence, drug-loaded HR-NPs exhibited high anti-tumor activity in vivo. Overall, the HR-NPs might have a potential as nanocarriers for drug delivery to treat hypoxia-associated diseases. (C) 2013 Elsevier Ltd. All rights reserved.
Keywords
GLYCOL CHITOSAN NANOPARTICLES; CANCER-THERAPY; POLY(ETHYLENE GLYCOL); FLUORESCENT MARKERS; BLOCK-COPOLYMERS; CELLS; DOXORUBICIN; CAMPTOTHECIN; MECHANISMS; CONJUGATE; GLYCOL CHITOSAN NANOPARTICLES; CANCER-THERAPY; POLY(ETHYLENE GLYCOL); FLUORESCENT MARKERS; BLOCK-COPOLYMERS; CELLS; DOXORUBICIN; CAMPTOTHECIN; MECHANISMS; CONJUGATE; Hypoxia; Nanoparticles; 2-Nitroimidazole; Bioreduction; Drug delivery
ISSN
0142-9612
URI
https://pubs.kist.re.kr/handle/201004/127142
DOI
10.1016/j.biomaterials.2013.11.022
Appears in Collections:
KIST Article > 2014
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