Controlled Delivery of Cytarabine in Sodium Carboxymethyl Cellulose/Copper-Doped Prussian Blue Hydrogels for Chemotherapy and Chemodynamic Therapy

To improve the therapy of chemotherapy for cancer treatment, hydrogels of sodium carboxymethyl cellulose (CMC)/copper-doped Prussian blue (CDPB) are synthesized for the controlled delivery of cytarabine (Cyt). CMC is connected to 3-aminophenylboronic acid (PBA) and dopamine (DA), respectively, by amidation reactions, and the obtained CMC-PBA and CMC-DA are cross-linked through boronate affinity for the encapsulation of CDPB and Cyt. The resultant CMC/CDPB/Cyt hydrogels can, respectively, respond to pH and H2O2, and thus, pH- and H2O2-responsive delivery of Cyt from the hydrogels is successfully achieved. More importantly, the overexpressed H2O2 in cancer cells can be converted to hydroxyl radicals (•OH) by the CDPB in the hydrogels through Fenton-like reactions, and the generated •OH can participate in the chemodynamic therapy (CDT) of cancers. Due to the combination treatment of chemotherapy and CDT, enhanced anticancer effects are obtained by using human acute promyelocytic leukemia (HL-60) cell lines as the model target.