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 (O-2) 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 O-2 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 O-2 for the electron on the Ti3C2 NSs to generate O-2(-) and OH through electron transfer. Furthermore, they also achieve O-1(2) generation through energy transfer due to O-2 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.