한빛사 논문
Thavasyappan Thambia,b, V.G. Deepagana,b, Hong Yeol Yoona,b,c, Hwa Seung Hana,b, Seol-Hee Kimd, Soyoung Sona,g, Dong-Gyu Jod,g, Cheol-Hee Ahne, Yung Doug Suhb,f, Kwangmeyung Kimc, Ick Chan Kwonc, Doo Sung Leea,b, Jae Hyung Parka,b,f,g,*
a Department of Polymer Science and Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea
b School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea
c Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea
d School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea
e Department of Materials Science and Engineering, Seoul National University, Seoul 151-744, Republic of Korea
f NanoBio Fusion Research Center, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea
g Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Suwon 440-746, Republic of Korea
*Corresponding author : Jae Hyung Park
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.
Keywords
Hypoxia; Nanoparticles; 2-Nitroimidazole; Bioreduction; Drug delivery
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