Intelligent Molybdenum Disulfide Complexes as a Platform for Cooperative Imaging‐Guided Tri‐Mode Chemo‐Photothermo‐Immunotherapy

Abstract Design of new nanoplatforms that integrates multiple imaging and therapeutic components for precision cancer nanomedicine remains to be challenging. Here, a facile strategy is reported to prepare polydopamine (PDA)‐coated molybdenum disulfide (MoS2) nanoflakes as a nanocarrier to load dual drug cisplatin (Pt) and 1‐methyl‐tryptophan (1‐MT) for precision tumor theranostics. Preformed MoS2 nanoflakes are coated with PDA, modified with methoxy‐polyethylene glycol (PEG)‐amine, and loaded with 1‐MT and Pt. The formed functional 1‐MT‐Pt‐PPDA@MoS2 (the second P stands for PEG) complexes exhibit good colloidal stability and photothermal conversion efficiency (47.9%), dual pH‐, and photothermal‐sensitive drug release profile, and multimodal thermal, computed tomography and photoacoustic imaging capability. Due to the respective components of Pt, MoS2, and 1‐MT that can block the immune checkpoint associated to tumoral indoleamine 2,3‐dioxygenase‐induced tryptophan metabolism, tri‐mode chemo‐photothermo‐immunotherapy of tumors can be realized. In particular, under the near infrared laser irradiation, fast release of both drugs can be facilitated to achieve cooperative tumor therapy effect, and the combined immunogenic cell death induced by the dual‐mode chemo‐photothermo treatment and the 1‐MT‐induced immune checkpoint blockade can boost enhanced antitumor immune response to generate significant cytotoxic T cells for tumor killing. The developed 1‐MT‐Pt‐PPDA@MoS2 complexes may be used as an intelligent nanoplatform for cooperative precision imaging‐guided combinational tumor therapy.