Synergistic TME-manipulation effects of a molybdenum-based polyoxometalate enhance the PTT effects on cancer cells

The intrinsic features of tumors often give rise to unsatisfactory outcomes of photothermal treatment (PTT). Remarkably, the tumor microenvironment (TME) with abundant antioxidants, elevated hydrogen peroxide (H2O2), and low pH has proven to be a tremendous obstacle for tumor treatment. Therefore, developing an effective photosensitizer that can respond to both NIR radiation and TME is imperative but remains a challenge. Here, we explore a molybdenum-based polyoxometalate (Na15[MoVI126-MoV28O462H14(H2O)70]·400H2O, [Mo154]) as a photosensitizer for TME-manipulated PTT enhancement because of the following features. Firstly, the 808 nm absorption of [Mo154] can be increased via pH-induced aggregation; secondly, due to the unique multi-electron property, [Mo154] can deplete cysteine and reactive oxygen species (ROS) via redox reactions; thirdly, reduced [Mo154] ([rMo154]) can further improve the 808 nm absorption by promoting the transition from Mo(VI) to Mo(V). Consequently, [Mo154] can overcome several obstacles in TME and thus improve the PTT efficiency by synergizing the effects of pH-induced aggregation, cysteine reduction and depletion, and free-radical scavenging. In addition to providing a promising photosensitizer for PTT, this finding extends the application of molybdenum-based polyoxometalates in the biomedical field.