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

Molybdenum disulfide (MoS2 ) 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 MoS2 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 MoS2 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 MoS2 nanosheets by the formation of disulfide bonds, which could further enhance the cellular uptake of DOX and MoS2 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 MoS2 (DOX-POVK-MoS2 -Tf) showed better a therapeutic effect than DOX-POVK-MoS2 and POVK-MoS2 , probably owing to the combined effects of target-directed uptake, acid-triggered drug release, and NIR induced localized heating, which suggest the designed MoS2 nanocarriers are promising for applications in multi-modal cancer therapy.