Hypoxia-responsive polymeric nanoparticles for tumor-targeted drug delivery

Title
Hypoxia-responsive polymeric nanoparticles for tumor-targeted drug delivery
Authors
Thavasyappan ThambiV.G. Deepagan윤홍열한화승김설희손소영조동규안철희Yung Doug Suh김광명권익찬이두성박재형
Keywords
Hypoxia; Nanoparticles; 2-Nitroimidazole; Bioreduction; Drug delivery
Issue Date
2014-02
Publisher
Biomaterials
Citation
VOL 35, NO 5, 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 derivativewas 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 DOXloaded 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 HRNPs might have a potential as nanocarriers for drug delivery to treat hypoxia-associated diseases.
URI
http://pubs.kist.re.kr/handle/201004/47258
ISSN
01429612
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KIST Publication > Article
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