Hypoxia-responsive polymeric nanoparticles for tumor-targeted drug delivery
- Hypoxia-responsive polymeric nanoparticles for tumor-targeted drug delivery
- Thavasyappan Thambi; V.G. Deepagan; 윤홍열; 한화승; 김설희; 손소영; 조동규; 안철희; Yung Doug Suh; 김광명; 권익찬; 이두성; 박재형
- Hypoxia; Nanoparticles; 2-Nitroimidazole; Bioreduction; Drug delivery
- Issue Date
- VOL 35, NO 5, 1735-1743
- 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.
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