GSH-Depleted Platinum(II) Metallacycles to Turn On the NIR Emission in Boosting Synergistic Cancer Therapy

Agents to combine functions simultaneously are highly needed but still challenging in synergistic therapy. Particularly, capabilities to deplete glutathione (GSH) in tumors and monitor their process are also important. Therefore, platinum(II) metallacycles are prepared by using aggregation-induced emission active ligands. Despite their similar structures, high emission for Mh1 is obtained (PLQY = 49.2%) in solids, but a PLQY of only 6.8% is recorded for Mh2. NIR emission in Mh2 can be turned-on in depleting GSH by releasing emissive ligands. Also, both type I and type II reactive oxygen species (ROS) are obtained in Mh2 nanoparticles. Due to the depletion of GSH and generation of ROS, oxidative stress in immunogenic cell death can be induced. By combining chemotherapy and photoimmunotherapy, synergistic therapy in vivo is obtained for Mh2-NPs to well inhibit the tumor growth, also showing antitumor immune effects in distant tumors. The work here provides some guidelines in designing the multi-functional agents, showing the great potentials in efficient cancer therapy.