Three Birds with One Stone: Acceptor Engineering of Hemicyanine Dye with NIR‐II Emission for Synergistic Photodynamic and Photothermal Anticancer Therapy

Abstract It is challenging to develop a near‐infrared (NIR) small molecular photosensitizer for synergistic phototherapy in deep tissues. Herein, first, a heavy‐atom‐free NIR hemicyanine photosensitizer (BHcy) for 808 nm light‐mediated synergistic photodynamic therapy/photothermal therapy (PDT/PTT) anticancer therapy by leveraging the acceptor engineering strategy is reported. This strategy endows BHcy with a more planar and larger π‐conjugated structure, resulting in long NIR absorption/emission at 770/915–1200 nm as well as enhanced singlet oxygen ( 1 O 2 ) generation ability and photothermal effect, which is ascribed to the reduced energy levels of excited singlet/triplet states and the promoted intersystem crossing process. Notably, BHcy‐based nanoparticles (BHcy‐NPs) exhibit efficient 1 O 2 yield (12.9%) and high photothermal conversion efficiency (55.1%). More importantly, BHcy‐NPs are able to significantly kill cancer cells by destroying main organelles and inhibit tumor growth in vivo after a single irradiation. Overall, this study provides a strategy to design new heavy‐atom‐free PDT/PTT agents for potential clinical applications.