Bottom-up synthesis of nanoflowers for combined PTT/TDT/ST therapy of osteosarcoma

As a common malignant bone tumor in adolescents, osteosarcoma (OS) possesses a very poor prognosis and lacks effective treatments. In this study, we developed a multifunctional nanotherapeutic agent (WSe 2 /AIPH/GOx) that can combine photothermal therapy (PTT) /thermodynamic therapy (TDT) /starvation therapy (ST) against OS. The prepared WSe 2 /AIPH/GOx exhibited a high photothermal conversion efficiency of 37.3% under 808 nm near-infrared laser irradiation, which could effectively eliminate tumor cells. In addition, the local high temperature caused by photothermal heat induces the rapid release and decomposition of AIPH, generating oxygen-independent alkyl radicals that promote tumor cell death in the hypoxic microenvironment. More importantly, the introduction of GOx depletes glucose to starve tumor cells on the one hand, and on the other hand can indirectly increase the thermal sensitivity of cells. In vivo experiments have demonstrated that WSe 2 /AIPH/GOx can effectively inhibit tumor growth in mice due to the combined effects of multiple therapies. Overall, this work provides an effective strategy for potential osteosarcoma treatment based on combination therapies.