A Target‐Directed Chemo‐Photothermal System Based on Transferrin and Copolymer‐Modified MoS 2 Nanoplates with pH‐Activated Drug Release

Molybdenum disulfide (MoS 2 ) nanosheets have attracted significant attention due to their photothermal properties, but the poor solubility and colloidal stability limited their further application in biomedical field. Here, we report a targeted photothermal controllable nanocarrier consisting of MoS 2 nanosheets modified with block copolymer P(OEG‐A)‐ b ‐P(VBA‐ co ‐KH570) and targeting ligand transferrin. P(OEG‐A)‐ b ‐P(VBA‐ co ‐KH570) is synthesized by RAFT polymerization and utilized not only to improve the solubility of MoS 2 nanosheets but also efficiently load the anti‐cancer drug doxorubicin (DOX) through an acid‐cleavable Schiff base linker. Thiol‐functionalized transferrin (Tf‐SH) is anchored onto the surface of MoS 2 nanosheets by the formation of disulfide bonds, which could further enhance the cellular uptake of DOX and MoS 2 to HepG2 cells for high‐efficiency synergetic therapy. The drug release experiments exhibited the minimal release of DOX at room temperature and neutral pH, and the maximal drug release of 53 % at acidic tumor pH and hyperthermia condition after 48 h. In addition, the DOX‐loaded, Tf‐SH and P(OEG‐A)‐ b ‐P(VBA‐ co ‐KH570) modified MoS 2 (DOX‐POVK‐MoS 2 ‐Tf) showed better a therapeutic effect than DOX‐POVK‐MoS 2 and POVK‐MoS 2 , probably owing to the combined effects of target‐directed uptake, acid‐triggered drug release, and NIR induced localized heating, which suggest the designed MoS 2 nanocarriers are promising for applications in multi‐modal cancer therapy.