Affiliation:
1. Clinical Medicine Scientific and Technical Innovation Center Shanghai Tenth People's Hospital Tongji University School of Medicine Shanghai 200092 P. R. China
2. Shanghai Frontiers Science Research Base of Intelligent Optoeletronics and Perception Institute of Optoelectronics Fudan University Shanghai 200433 P. R. China
3. South Australian immunoGENomics Cancer Institute Faculty of Health and Medical Sciences The University of Adelaide Adelaide South Australia 5005 Australia
Abstract
AbstractIn situ vaccine (ISV) can provoke systemic anti‐tumor immunity through the induction of immunogenic cell death (ICD). The development of ISV technology has been restricted by the limited and suboptimal ICD driven tumor antigen production which are currently relying on chemo‐drugs, photo‐/radio‐sensitizers, oncolytic‐virus and immunostimulatory agents. Herein, a sulfate radical (SO4·−) based ISV is reported that accomplishes superior tumor immunotherapy dispense from conventional approaches. The ISV denoted as P‐Mn‐LDH is constructed by intercalating peroxydisulfate (PDS, a precursor of SO4·−) into manganese layered double hydroxide nanoparticles (Mn‐LDH). This design allows the stabilization of PDS under ambient condition, but triggers a Mn2+ mediated PDS decomposition in acidic tumor microenvironment (TME) to generate in situ SO4·−. Importantly, it is found that the SO4·‐ radicals not only effectively kill cancer cells, but also induce a necroptotic cell death pathway, leading to robust ICD signaling for eliciting adaptive immunity. Further, the P‐Mn‐LDH can activate the stimulator of interferon genes (STING) pathway to further boost anti‐tumor immunity. Collectively, the P‐Mn‐LDH based ISV exhibited potent activity in inhibiting tumor growth and lung metastasis. When combined with immune checkpoint inhibitor, significant inhibition of distant tumors is achieved. This study underpins the promise of SO4·‐ based vaccine technology for cancer immunotherapy.