Heteroatom Acceptor Engineering Boosts NIR‑II Phototheranostics of Quinoid–Donor–Acceptor Semiconducting Polymers

ABSTRACT Multimodal phototheranostics utilizing a single, integrated molecular platform represents a streamlined and efficient strategy for precise cancer therapy. Herein, we first report a rationally engineered quinoid–donor–acceptor (Q–D–A) molecule, designated PAQM‐PT, through deliberate heteroatom acceptor modulation. This designed system concurrently delivers absorption redshift, reduced aggregation tendency, and second near‐infrared (NIR‐II) emission enhancement. The resulting PAQM‐PT nanoparticles (NPs) exhibit an excellent molar extinction coefficient ( ε ) of 2.82 × 10 5 M − 1 cm − 1 and decent fluorescence quantum yield (FLQY) of 0.054%, boosting NIR‐II brightness to 152.28 M − 1 cm − 1 ( ε × FLQY). Furthermore, under 808 nm laser irradiation (1.0 W cm − 2 ), PAQM‐PT NPs show an extremely high photothermal conversion efficiency (PCE) of 87.3%. This work reports a breakthrough polymer that combines strong NIR‐II fluorescence brightness with high PCE—a dual achievement previously unreported for polymeric agents. These properties enable precise tumor delineation and effective tumor ablation without any relapses with high biosafety via NIR‐II fluorescence imaging (FLI)–photoacoustic imaging (PAI)–photothermal imaging (PTI) trimodal to guided photothermal therapy (PTT) in an orthotopic mouse breast tumor model. This work not only presents a pioneering Q–D–A‐type phototheranostic agent with multimodal imaging but also provides a new design perspective for developing high‐performance phototheranostic systems for practical cancer treatment.