基于近红外光的 BiS/TiC-TPP 纳米杂化结构用于乏氧肿瘤的光动力学治疗与光热治疗联合

BACKGROUND: Photodynamic therapy (PDT) efficacy of bismuth sulfide (BiS) semiconductor has been severely restricted by its electron-hole pairs (e-h) separation inefficiency and oxygen (O) deficiency in tumors, which greatly hinders reactive oxygen species (ROS) generation and further clinical application of BiS nanoparticles (NPs) in biomedicine. RESULTS: Herein, novel BiS/titanium carbide (TiC) two-dimensional nano-heterostructures (NHs) are designed to realize multimode PDT of synchronous O self-supply and ROS generation combined with highly efficient photothermal tumor elimination for hypoxic tumor therapy. BiS/TiC NHs were synthesized via the in situ synthesis method starting from TiC nanosheets (NSs), a classical type of MXene nanostructure. Compared to simple BiS NPs, BiS/TiC 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 BiS can react with water to supply O for the electron on the TiC NSs to generate ·O and ·OH through electron transfer. Furthermore, they also achieve O generation through energy transfer due to O self-supply. After the modification of triphenylphosphium bromide (TPP) on BiS/TiC 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 BiS-based nanoplatforms, providing a new strategy for hypoxic tumor theranostics.

背景：硫化铋（BiS）半导体的光动力疗法（PDT）疗效受到其电子-空穴对（e-h）分离效率低和肿瘤中氧气（O）缺乏的严重限制，这极大地阻碍了活性氧（ROS）的产生，进一步限制了 BiS 纳米粒子（NPs）在生物医学中的临床应用。

结果：本文设计了新型 BiS/碳化钛（TiC）二维纳米异质结构（NHs），以实现同步 O 自供给和 ROS 生成的多模式 PDT，并结合高效的光热肿瘤消除来实现缺氧肿瘤治疗。BiS/TiC NHs 是通过从 TiC 纳米片（NSs）开始的原位合成方法合成的，TiC NSs 是一种典型的 MXene 纳米结构。与简单的 BiS NPs 相比，BiS/TiC NHs 通过提高光生载流子分离，显著扩展了吸收至近红外（NIR）区域，并增强了光催化活性，其中 BiS 的价带（VB）上的空穴可以与水反应，通过电子转移为 TiC NSs 上的电子提供 O 以生成·O 和·OH。此外，它们还通过能量转移实现 O 生成，因为可以自供给 O。在对 BiS/TiC NHs 进行三苯基膦溴（TPP）修饰后，进行了系统的体外和体内评估，结果表明，该纳米平台的协同治疗效果可通过近红外激光照射完全消除 U251 肿瘤而无复发，并且由于具有很强的 X 射线衰减能力，可用于计算机断层扫描（CT）成像。

结论：这项工作扩展了基于 BiS 的纳米平台的光疗效果，为缺氧肿瘤治疗提供了新的策略。