Hypoxia-Induced Drug Release or Exposure of Positive Charge

1 Hypoxia-Induced Drug Release or Exposure of Positive Charge 

Conjugation of a 2-nitroimidazole derivative to carboxymethyl dextran allowed doxorubicin-loading with hypoxia-induced cellular uptake and cytotoxicity in vitro [110]. The dextran group for stability in the circulation and primary tumor accumulation was combined with conversion from a hydrophobic 2-nitroimidazole to a hydrophilic 2-aminoimidazole under hypoxia to promote doxorubicin release in tumor environment. This system showed a 4-fold doxorubicin accumulation in tumor over liver, lung, spleen, kidney, and heart 24 h after systemic injection and enhanced anticancer activity in vivo over free drug. 

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