Activable nano-immunomodulator assembled from π-extended naphthalenediimide for precision photothermal immunotherapy

• Main Authors: Zhong, Wenbin, Yuan, Wei, Chen, Yun, Ma, Zhaoyu, Ma, Mengmeng, Tan, Brynne Shu Ni, Yang, Jie, Zhao, Yanli
• Other Authors: School of Chemistry, Chemical Engineering and Biotechnology
• Format: Article
• Language: English
• Published: 2024
• Subjects: Medicine, Health and Life Sciences; Glutathione activable effect; Photothermal immunotherapy
• Online Access: https://hdl.handle.net/10356/179257
• Institution: Nanyang Technological University

A nano-immunomodulator (R-NPT NP) comprising a tumor microenvironment (TME) activable resiquimod (R848) and a π-extended NIR-absorbing naphthophenanthrolinetetraone (NPT) has been engineered for spatiotemporal controlled photothermal immunotherapy. R-NPT NP demonstrated excellent photostability, while R848 promoted synergistic immunity as a toll-like receptor 7/8 (TLR7/8) agonist. Upon accumulation at the tumor site, R-NPT NP released R848 in response to redox metabolite glutathione (GSH), triggering dendritic cell (DC) activation. The photothermal effect endowed by R-NPT NP can ablate tumors directly and trigger immunogenic cell death to augment immunity after photoirradiation. The synergistic effect of GSH-liable TLR7/8 agonist and released immunogenic factors leads to a robust evocation of systematic immunity through promoted DC maturation and T cell infiltration. Thus, R-NPT NP with photoirradiation achieved 99.3 % and 98.2 % growth inhibition against primary and distal tumors, respectively.