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

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 O₂ ) 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 O₂ 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.