Activable Nano‐Immunomodulator Assembled from π‐Extended Naphthalenediimide for Precision Photothermal Immunotherapy

Abstract 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.