Achieving Efficient NIR‐II Type‐I Photosensitizers for Photodynamic/Photothermal Therapy upon Regulating Chalcogen Elements

Abstract Second near‐infrared (NIR‐II) window type‐I photosensitizers have intrinsic advantages in photodynamic/photothermal therapy (PDT/PTT) of some malignant tumors with deep infiltration, large size, complicated location, and low possibility of surgery/radiotherapy. Herein, three chalcogen‐element‐based donor–acceptor‐type semiconducting polymers (poly[2,2″‐(( E )‐4,4″‐bis(2‐octyldodecyl)‐[6,6″‐bithieno[3,2‐ b ]pyrrolylidene]‐5,5″(4 H ,4″ H )‐dione)‐ alt ‐2,5‐(thiophene)] (PTS), poly[2,2″‐(( E )‐4,4″‐bis(2‐octyldodecyl)‐[6,6″‐bithieno[3,2‐ b ]pyrrolylidene]‐5,5″(4 H ,4″ H )‐dione)‐ alt ‐2,5‐(selenophene)] (PTSe), and poly[2,2″‐(( E )‐4,4″‐bis(2‐octyldodecyl)‐[6,6″‐bithieno[3,2‐ b ]pyrrolylidene]‐5,5″(4 H ,4′ H )‐dione)‐ alt ‐2,5‐(tellurophene)] (PTTe)) are synthesized and fully characterized, demonstrating strong absorption in the NIR‐II region. Upon adjusting the chalcogen elements, the intramolecular charge‐transfer characteristics and the heavy‐atom effect are tuned to enhance the intersystem crossing rate, improving the photodynamic effect. Moreover, the energy levels and Gibbs free energies are tuned to facilitate the type‐I photodynamic process. As a result, PTTe nanoparticles (NPs) produce superoxide anion radicals (O 2 •− ) more efficiently and demonstrate higher photothermal conversion efficiency than PTS and PTSe NPs upon NIR‐II (1064 nm) laser irradiation, exhibiting unprecedented NIR‐II type‐I PDT/PTT performance in vitro and in vivo. This work provides ideas for achieving high‐performance NIR‐II type‐I PDT/PTT semiconducting polymers for hypoxic oncotherapy.