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

Li, Xing-Wang; Huang, Yongkang; Fang, Han; Wang, Han-Yu; Sun, He; Yu, Mei-Hui; Du, Yaping; Chang, Ze et al. · Nano Lett · 2025

basic_science · Level V

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Abstract

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 [M<sub>6</sub>L<sub>4</sub>] cages based on a 2,4,6-tri(2-pyridine-4-yl)-1,3,5-triazine (TPT) acceptor and M(bpy)<sup>2+</sup> (M = Pd for <b>1a</b>, Pt for <b>1b</b>) nodes were functionalized with tetrathiafulvalene (TTF) to form <b>TTF@1a</b> and <b>TTF@1b</b>. This D-A functionalization enhanced charge transfer, extending absorption into the near-infrared region with photothermal conversion efficiencies of 35.65% for <b>TTF@1a</b> and 40.65% for <b>TTF@1b</b>. 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. <i>In vitro</i> and <i>in vivo</i> tests demonstrated the effectiveness of this synergistic approach for antitumor applications.