ZIF-8 coated gold nanospheres: A multi-responsive drug delivery system promoting the killing effect of photothermal therapy against osteosarcoma cells

Photothermal therapy (PTT) has been widely used in the treatment of tumors, but its efficacy is greatly limited by the inability of precise drug delivery and the increase of heat shock proteins (HSPs) caused by high temperature. This article describes a therapeutic strategy to enhance PTT with starvation therapy in conjunction with ferroptosis mechanism. A nanoparticle platform ZIF-8@GA was constructed by wrapping together glucose oxidase (GOX) and gold nanospheres (AuNPs) loaded with dihydroartemisinin (DHA) with zeolitic imidazolate framework-8 (ZIF-8). This platform can take advantage of the micro-environment of osteosarcoma (OS) cells, featuring low pH and high reactive oxygen species (ROS), for precision drug delivery. GOX can effectively catalyze glucose to produce gluconic acid and H₂O₂, and DHA can also induce ROS production in OS cells. ROS produced by GOX and DHA can further generate lipid peroxidation (LPO) and lead to ferroptosis of OS cells. At the same time, ROS and LPO produced can inhibit the expression of HSPs, thereby increasing the therapeutic effect of PTT. In vitro experiments show that the nanoparticles are pH and ROS responsive. 1 μg/mL GOX combined with 0.2 μg/mL DHA promotes ferroptosis of OS cells, and increases the killing effect of near-infrared (NIR) on OS cells. Further in vivo experiments showed that the nano drug-delivery platform combined with PTT can effectively inhibit the growth of OS cells. Meanwhile, this study provides a new idea for the treatment of OS with biomaterials combined with various treatment methods.