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

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 ''(4H,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 ''(4H,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 ''(4H,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(center dot-)) 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.

Automated summary

This study synthesized three chalcogen-element-based donor-acceptor-type semiconducting polymers and tuned their properties to enhance photodynamic effects and superoxide anion generation efficiency, demonstrating unprecedented high-performance in vitro and in vivo.