Multifunctional Nanosystem for Synergistic Tumor Therapy Delivered by Two-Dimensional MoS₂

A multifunctional nanosystem based on two-dimensional molybdenum disulfide (MoS₂) was developed for synergistic tumor therapy. MoS₂ was stabilized with lipoic acid (LA)-modified poly(ethylene glycol) and modified with a pH-responsive charge-convertible peptide (LA-K₁₁(DMA)). Then, a positively charged photosensitizer, toluidine blue O (TBO), was loaded on MoS₂ via physical absorption. The negatively charged LA-K₁₁(DMA) peptide was converted into a positively charged one under acidic conditions. Charge conversion of the peptide could reduce the binding force between positively charged TBO and MoS₂, leading to TBO release. Furthermore, the positively charged nanosystem was easily endocytosed by cells. Photo-induced hyperthermia of MoS₂ in the tumor areas could promote TBO release and exhibited photothermal therapy. In vitro and in vivo results demonstrated that fluorescence and photo-induced reactive oxygen species (ROS) generation of TBO were severely decreased by MoS₂ under normal conditions. While in the acidic condition, the pH-responsive nanosystem exhibited a highly specific and efficient antitumor effect with TBO release and photo-induced ROS generation, suggesting to be a promising accessory for synergistic tumor therapy.