Artesunate loaded core-shell nanoplatform for the chemo-chemodynamic-photothermal synergistic cancer therapy

To improve the treatment efficiency and targeted enrichment ability of tumors, in this study, a nanoplatform (Fe_xCu_ySe@MONs-ART@HA) based iron copper selenide@mesoporous organosilica nanoparticles (Fe_xCu_ySe@MONs) has been designed for synergistic chemotherapy (CT), photothermal therapy (PTT), and chemodynamic therapy (CDT). The photothermal performance and peroxidase-like activity of Fe_xCu_ySe@MONs generated PTT-CDT synergistic therapy. The densely coated hyaluronic acid (HA) layers on the surface of Fe_xCu_ySe@MONs not only improved the cancer-targeting efficiency but also prevented the nonspecific release of artesunate (ART). The high concentration of glutathione (GSH) and acid tumor microenvironment triggered the release of ART for chemotherapy, which simultaneously augmented the CDT efficiency of Fe_xCu_ySe@MONs. Additionally, the glutathione peroxidase 4 (GPX4) levels significantly declined. MTT assay results indicated that Fe_xCu_ySe@MONs-ART@HA demonstrates superior cytotoxic effects compared to Fe_xCu_ySe@MONs@HA and ART alone. Furthermore, cells viability decreased to 18.75 % upon the application of an 808 nm laser. In vivo investigations further revealed that the Fe_xCu_ySe@MONs-ART@HA + laser treatment group exhibited the highest rate of tumor growth inhibition, TGI% value reaching nearly 87.3 %, which was much higher than the 31.2 %, 45.6 % and 76.5 % in the groups of ART, Fe_xCu_ySe@MONs@HA and Fe_xCu_ySe@MONs@HA + laser. Owing to the synergistic effect, this nanoplatform significantly improved antitumor efficacy with minimal toxicity both in vitro and in vivo. These findings highlight such a CT-PTT-CDT synergistic drug delivery system showed great potential for treating tumors.