▎ 摘　　要

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. & COPY; 2023 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).