Bimetal-biligand frameworks for spatiotemporal nitric oxide-enhanced sono-immunotherapy

• Main Authors: Cheng, Yu, Zhong, Wenbin, Chen, Yun, Tan, Brynne Shu Ni, Zhao, Yue, Guo, Jingjing, Ma, Mengmeng, Zhao, Yanli
• Other Authors: School of Chemistry, Chemical Engineering and Biotechnology
• Format: Article
• Language: English
• Published: 2024
• Subjects: Engineering; Bimetal-biligand frameworks; Cancer treatment
• Online Access: https://hdl.handle.net/10356/181216
• Institution: Nanyang Technological University

Sonodynamic therapy can trigger immunogenic cell death to augment immunotherapy, benefiting from its superior spatiotemporal selectivity and non-invasiveness. However, the practical applications of sonosensitizers are hindered by their low efficacy in killing cancer cells and activating immune responses. Here, two US Food and Drug Administration-approved drug ligands (ferricyanide and nitroprusside) and two types of metals (copper/iron) are selected to construct a bimetal-biligand framework (Cu[PBA-NO]). Through elaborate regulation of multiple metal/ligand coordination, the systemically administered Cu[PBA-NO] nanoagent shows sono-catalytic and NO release ability under ultrasound irradiation, which can be used for effective sono-immunotherapy. Moreover, Cu[PBA-NO] can downregulate intracellular glutathione levels that would destroy intracellular redox homeostasis and facilitate reactive oxygen species accumulation. The released tumor-associated antigens subsequently facilitate dendritic cell maturation within the tumor-draining lymph node, effectively initiating a T cell-mediated immune response and thereby bolstering the capacity to identify and combat cancer cells. This study paves a new avenue for the efficient cancer sono-immunotherapy.