Construction of a dual-drug delivery system based on oxidized alginate and carboxymethyl chitosan for chemo-photothermal synergistic therapy of osteosarcoma

Abstract

A dual-drug delivery system (DDDS) based on oxidized alginate (OxAlg) and carboxymethyl chitosan (CMCS) is developed, which can be used for dual-responsive delivery of methotrexate (MTX) and naringin (Nar) for efficient treatment of osteosarcoma. Nar is first loaded onto graphene oxide (GO) through π-π stacking and hydrogen bonding, and then the Nar loaded GO (GO/Nar) is co-encapsulated with MTX by the hydrogel of OxAlg and CMCS generated through Schiff base reaction. The acylhydrazone (–N = C–) bonds between OxAlg and CMCS are prone to be hydrolyzed in an acidic medium, speeding the delivery of the two drugs; meanwhile, GO in this DDDS is an outstanding photothermal agent, leading to near-infrared light (NIR)-responsive delivery of the two drugs. The cumulative release of MTX and Nar can reach 91.09% and 85.69%, respectively, at pH 5.0 with NIR irradiation. The produced hyperthermia under NIR irradiation can result in the ablation of the osteosarcoma cells, and thus the therapeutic efficacy of the DDDS against osteosarcoma is significantly improved via the chemo-photothermal synergistic therapy mode, which can be further confirmed by the cytotoxicity test.