Diradical‐Featured Organic Small‐Molecule Photothermal Material Based on 4,6‐di(2‐thienyl)thieno[3,4‐c][1,2,5]thiadiazole for Photothermal Immunotherapy

Abstract Photothermal immunotherapy can provide an efficient and convenient strategy for cancer treatment by inducing immunogenic cell death (ICD) to generate vaccine‐like functions in situ, which highly relies on suitable photothermal agents with superior photothermal effect. Herein, a novel diradical‐featured organic small‐molecule photothermal material (TTD‐TPE) based on 4,6‐di(2‐thienyl)thieno[3,4‐c][1,2,5]thiadiazole and tetraphenylethylene is developed to exhibit near‐infrared (NIR) absorption of 808 nm, high photothermal conversion efficiency (PTCE) of about 75%, and superior photoacoustic imaging (PAI) property in nanoparticle. The excellent photothermal effect of TTD‐TPE nanoparticles originates from the integrated synergic effect of D–A interactions, diradical character, and excited‐state intramolecular motion, which not only ablates the primary tumor by localized high temperature but also transforms the primary tumor into vaccine in situ through ICD to inhibit the growth of distant and metastatic tumors, demonstrating the huge potential in photothermal immunotherapy. Thus, this finding encourage researchers to develop superior organic small‐molecule photothermal materials to boost the simple but useful modality for cancer treatment.