Bi₂S₃/Ti₃C₂-TPP nano-heterostructures induced by near-infrared for photodynamic therapy combined with photothermal therapy on hypoxic tumors

Background: Photodynamic therapy (PDT) efficacy of bismuth sulfide (Bi₂S₃) semiconductor has been severely restricted by its electron–hole pairs (e⁻−h⁺) separation inefficiency and oxygen (O₂) deficiency in tumors, which greatly hinders reactive oxygen species (ROS) generation and further clinical application of Bi₂S₃ nanoparticles (NPs) in biomedicine. Results: Herein, novel Bi₂S₃/titanium carbide (Ti₃C₂) two-dimensional nano-heterostructures (NHs) are designed to realize multimode PDT of synchronous O₂ self-supply and ROS generation combined with highly efficient photothermal tumor elimination for hypoxic tumor therapy. Bi₂S₃/Ti₃C₂ NHs were synthesized via the in situ synthesis method starting from Ti₃C₂ nanosheets (NSs), a classical type of MXene nanostructure. Compared to simple Bi₂S₃ NPs, Bi₂S₃/Ti₃C₂ NHs significantly extend the absorption to the near-infrared (NIR) region and enhance the photocatalytic activity owing to the improved photogenerated carrier separation, where the hole on the valence band (VB) of Bi₂S₃ can react with water to supply O₂ for the electron on the Ti₃C₂ NSs to generate ·O₂⁻ and ·OH through electron transfer. Furthermore, they also achieve ¹O₂ generation through energy transfer due to O₂ self-supply. After the modification of triphenylphosphium bromide (TPP) on Bi₂S₃/Ti₃C₂ NHs, systematic in vitro and in vivo evaluations were conducted, revealing that the synergistic-therapeutic outcome of this nanoplatform enables complete eradication of the U251 tumors without recurrence by NIR laser irradiation, and it can be used for computed tomography (CT) imaging because of the strong X-ray attenuation ability. Conclusion: This work expands the phototherapeutic effect of Bi₂S₃-based nanoplatforms, providing a new strategy for hypoxic tumor theranostics.