Investigation of Thermally Induced Cellular Ablation and Heat Response Triggered by Planar MoS₂-Based Nanocomposite

In comparison to conventional tumor treatment methods, photothermal therapy (PTT) is one of the innovative therapeutic strategies that employs light to produce localized heat for targeted ablation of cancer cells. Among the various kinds of heat generation nanomaterials, transition metal dichalcogenide nanosheets, especially molybdenum disulfide (MoS₂), have recently been investigated as one of the promising PTT candidates because of their strong absorbance in the near-infrared (NIR) tissue transparency window and excellent photothermal conversion capability. In line with the great potential of MoS₂-based nanomaterials in biomedical applications, their intrinsic therapeutic performance and corresponding cellular response are required to be continually investigated. In order to further improve MoS₂-based PTT efficacy and dissect the molecular mechanism during heat stimuli, in this study, we successfully designed a novel and effective PTT platform by integration of MoS₂ nanosheets with peptide-based inhibition molecules to block the function of heat shock proteins (Hsp90), one type of chaperone proteins that play protective roles in living systems against cellular photothermal response. Such a combined nanosystem could effectively induce cell ablation and viability assays indicated approximately 5-fold higher PTT treatment efficacy (8.8% viability) than that of MoS₂ itself (48% viability) upon 808 nm light irradiation. Moreover, different from the case based on MoS₂ alone that could cause tumor ablation through the process of necrosis, the detailed mechanism analysis revealed that the inhibition of Hsp90 could significantly increase the photothermally mediated apoptosis, hence resulting in remarkable enhancement of photothermal treatment. Such promising studies provide the great opportunity to better understand the cellular basis of light-triggered thermal response. Moreover, they can also facilitate the rational design of new generations of PTT platforms toward future theranostics.