Abstract
BACKGROUND: Photodynamic therapy (PDT) efficacy of bismuth sulfide (Bi(2)S(3)) 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 Bi(2)S(3) nanoparticles (NPs) in biomedicine. RESULTS: Herein, novel Bi(2)S(3)/titanium carbide (Ti(3)C(2)) 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. Bi(2)S(3)/Ti(3)C(2) NHs were synthesized via the in situ synthesis method starting from Ti(3)C(2) nanosheets (NSs), a classical type of MXene nanostructure. Compared to simple Bi(2)S(3) NPs, Bi(2)S(3)/Ti(3)C(2) 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 Bi(2)S(3) can react with water to supply O(2) for the electron on the Ti(3)C(2) NSs to generate ·O(2)(-) and ·OH through electron transfer. Furthermore, they also achieve (1)O(2) generation through energy transfer due to O(2) self-supply. After the modification of triphenylphosphium bromide (TPP) on Bi(2)S(3)/Ti(3)C(2) 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 Bi(2)S(3)-based nanoplatforms, providing a new strategy for hypoxic tumor theranostics.