Regulated cell death-amplified sonodynamic anti-tumor immune nanotherapeutics

Nanomedicine-assisted sonodynamic therapy (SDT) has emerged as one of the most promising cancer therapies due to its unique advantages of high penetration, non-radiation, and excellent oxidative stress effect, but has always suffered from the self-protection mechanism and apoptosis resistance characteristics of evolutionarily mutated cancer cells. Regulated cell death (RCD) has received increasing attention in precision cancer treatments because of its significant role in synergistically sensitizing apoptosis and reversing the immunosuppressive microenvironment during SDT nanomedicine-triggered immunogenic cell death. Herein, paradigmatic research of RCD-augmented sonodynamic tumor immunotherapeutics are typically introduced, such as autophagy blockade, ferroptosis targeting, pyroptosis induction, necroptosis initiation, cuproptosis actuation, PANoptosis trigger, and the coordinated anti-tumor mechanisms are discussed in detail. Multiple analysis focusing on the currently unsolved problems and future development prospects of RCD-based SDT nano-oncology medicine are also discussed and prospected to further strengthen and expand the scope of its therapeutic applications. Emerging RCD-augmented sonodynamic tumor immunotherapeutics, such as autophagy blockade, ferroptosis targeting, pyroptosis induction, necroptosis initiation, cuproptosis actuation, and PANoptosis trigger, coordinately enhanced the anti-tumor effects through apoptosis sensitization mechanisms and deeply expanded the scope of sonodynamic anti-tumor therapeutic applications. image