Na2S2O8 Nanoparticles Trigger Antitumor Immunotherapy through Reactive Oxygen Species Storm and Surge of Tumor Osmolarity.
Yang LiuWenyao ZhenYinghui WangShu-Yan SongHong-Jie ZhangPublished in: Journal of the American Chemical Society (2020)
Although more attention has been attracted to the therapy based on reactive oxygen species (ROS) for tumor therapy in recent years, such as photodynamic therapy and chemodynamic therapy, the limited ROS production rate leads to their poor treatment effect owing to the relatively low content of O2 and H2O2 in tumor microenvironments, confined light penetration depth, strict Fenton reaction conditions (pH 3-4), and so on. Therefore, it is urgent to explore the new agents with highly efficient ROS generation capacity. Herein, we first prepared phospholipid coated Na2S2O8 nanoparticles (PNSO NPs) as new ROS generation agents for in situ generating Na+ and S2O82- through gradual degradation, which can then be changed to toxic •SO4- (a novel reported ROS) and •OH regardless of the amount of H2O2 and pH value in the tumor microenvironment (TME). As the generation of a large amount of Na+, PNSO NPs can bypass the ion transport rules of cells through endocytosis to deliver large amounts of Na+ into the cells, resulting in a surge of osmolarity and rapid cell rupture and lysis. Osmotic pressure induced by PNSO NPs will further lead to an unusual manner of cell death: caspase-1-related pyroptosis. Moreover, all of above effects will cause high immunogenic cell death, regulate the immunosuppressed TME, and then activate systemic antitumor immune responses to combat tumor metastasis and recurrence. We believe PNSO NPs will be new and potential ROS generation agents, and this work will broaden the thinking of the exploring of new antitumor nanodrugs.
Keyphrases
- cell death
- reactive oxygen species
- cell cycle arrest
- induced apoptosis
- highly efficient
- photodynamic therapy
- dna damage
- immune response
- working memory
- hydrogen peroxide
- cell proliferation
- single cell
- wastewater treatment
- bone marrow
- oxidative stress
- drug induced
- pi k akt
- climate change
- replacement therapy
- quantum dots