Donor–Acceptor Functionalized Water-Soluble Metal–Organic Cages Showing an Excellent Synergistic Photothermal–Chemotherapy Effect

Water-soluble metal-organic cages (WSMOCs) show high potential as antitumor agents, while the targeted functionalization of WSMOCs toward enhanced antitumor performances is a challenging task. Herein, WSMOCs were functionalized with donor-acceptor (D-A) systems for synergistic photothermal-chemotherapy. Octahedral [M₆L₄] cages based on a 2,4,6-tri(2-pyridine-4-yl)-1,3,5-triazine (TPT) acceptor and M(bpy)²⁺ (M = Pd for 1a, Pt for 1b) nodes were functionalized with tetrathiafulvalene (TTF) to form TTF@1a and TTF@1b. This D-A functionalization enhanced charge transfer, extending absorption into the near-infrared region with photothermal conversion efficiencies of 35.65% for TTF@1a and 40.65% for TTF@1b. Also, the D-A functionalization was found to enhance the stability of the compound and induce their aggregation into nanoparticles to increase their cellular compatibility. Additionally, the acidic-sensitive ion release feature of the compounds made them promising for targeted chemotherapy. In vitro and in vivo tests demonstrated the effectiveness of this synergistic approach for antitumor applications.