A tri-responsive dual-drug delivery system based on mesoporous silica nanoparticles@polydopamine@graphene oxide nanosheets for chemo-photothermal therapy of osteosarcoma

Abstract

A pH, redox and near infrared (NIR) irradiation tri-responsive dual-drug delivery system (DDDS) is constructed for the treatment of osteosarcoma. Methotrexate (MTX) is encapsulated into the mesoporous silica nanoparticles (MSNs) by polydopamine (PDA), and then the core–shell structured MTX/MSNs@PDA is embedded into the graphene oxide (GO) nanosheets to further enhance the photothermal conversion capability of this system. The resultant MTX/MSNs@PDA@GO is co-encapsulated with naringin (Nar) into the hydrogels of carboxymethyl cellulose (CMC) and cystamine (Cys) generated through amidation reaction. The disulfide linkage (–S–S–) in Cys can be reduced to sulphydryl groups (–SH) by glutathione (GSH), resulting in the degradation of the hydrogels; on the other hand, both PDA and the amide linkage between CMC and Cys are pH-sensitive. Therefore, the constructed DDDS can be used for pH-, redox- and NIR irradiation-responsive delivery of MTX and Nar. Finally, the validity of the developed DDDS is evaluated by cytotoxicity test.