Nanoparticle-driven reactive oxygen species therapy: A new frontier in osteosarcoma treatment

Reactive oxygen species (ROS) play a critical role in osteosarcoma (OS) therapy by inducing programmed cell death when their levels exceed the cellular threshold. Due to their inherently elevated ROS levels, OS cells are more susceptible to ROS upregulation than normal bone cells, offering a therapeutic window for selective cancer cell elimination. However, the intrinsic antioxidant defense mechanisms in OS cells mitigate the effects of conventional ROS-generating agents, limiting their clinical efficacy. To overcome this challenge, nanoparticlebased strategies have been developed to enhance ROS production and improve therapeutic outcomes. Despite significant progress, a comprehensive framework for designing and optimizing ROS-generating nanoplatforms for OS treatment remains lacking. This review systematically classifies ROS-upregulating nanoparticles based on their underlying mechanisms of action and discusses their therapeutic potential. Additionally, key challenges and future directions are highlighted to guide the development of next-generation nanomaterials for OS therapy.