Figure 13.

Hypoxia-responsive drug delivery. (A) Dual-stimuli-sensitive nanoparticles prepared from polyethyleneimine-nitroimidazole micelles (PEI-NI) co-assembled with Ce6-linked hyaluronic acid (HC). Hypoxia-mediated activation was achieved by the incorporation of a hypoxia-responsive electron acceptor (nitroimidazole, NI) converted to hydrophilic 2-aminoimidazole under hypoxic conditions leading to the release of nanoparticle-loaded doxorubicin. (B) CD 44-mediated targeted delivery of doxorubicin in cancer stem cells and release of DOX in response to hypoxia generated by laser irradiation. CD44 is a cell surface receptor, which is overexpressed in most of the cancer stem cells. Hyaluronic acid (HA), a strong affinity ligand for CD 44, is usually decorated on the surface of nanoparticles for recognizing and binding to the cancer stem cell leading to the delivery of the drug to the specific tumor cell. Reproduced with permission [116].