Synchronization of Tumor Oxygenation and Metabolic Windows to Enhance Immunogenic Cell Death in Photodynamic and Sonodynamic Cancer Therapy

Abstract

Photodynamic therapy (PDT) and sonodynamic therapy (SDT) have become the most least invasive forms of cancer treatment that can achieve immunogenic cell death (ICD). Nevertheless, their therapeutic efficacy is grossly limited by tumor hypoxia and tumor metabolic reprogramming in the tumor microenvironment. More current developments in nanomedicine have allowed a very high degree of spatiotemporal control of oxygenation and metabolic activity levels, which has generated transient therapeutic windows allowing increased reactive oxygen species production and augmentation of ICD. This is a systematic review of the mechanistic interplay between the tumor oxygen dynamics, metabolic remodeling, and immune activation in PDT- and SDT-based cancer therapies. We point out oxygen-producing and regulative metabolic nanoplatforms that coordinate these windows to overcome immune suppression, stimulate dendritic cells, as well as establish long-term antitumor immunity. Lastly, we comment on the translational challenges and future opportunities to combine synchronized oxygen -metabolic modulation with multimodal and immunotherapeutic interventions and position PDT and SDT as the future systemic cancer immunotherapies.