Applications of Boron Cluster Supramolecular Frameworks as Metal-Free Chemodynamic Therapy Agents for Melanoma.

Chemodynamic therapy (CDT) is a highly targeted approach to treat cancer since it converts hydrogen peroxide into harmful hydroxyl radicals (OH·) through Fenton or Fenton-like reactions. However, the systemic toxicity of metal-based CDT agents has limited their clinical applications. Herein, a metal-free CDT agent: 2,4,6-tri(4-pyridyl)-1,3,5-triazine (TPT)/ [closo-B 12 H 12 ] 2- (TPT@ B 12 H 12 ) is reported. Compared to the traditional metal-based CDT agents, TPT@B 12 H 12 is free of metal avoiding cumulative toxicity during long-term therapy. Density functional theory (DFT) calculation revealed that TPT@B 12 H 12 decreased the activation barrier more than 3.5 times being a more effective catalyst than the Fe 2+ ion (the Fenton reaction), which decreases the barrier about twice. Mechanismly, the theory calculation indicated that both [B 12 H 12 ] -· and [TPT-H] 2+ have the capacity to decompose hydrogen into 1 O 2 , OH·, and O 2 -· . With electron paramagnetic resonance and fluorescent probes, it is confirmed that TPT@B 12 H 12 increases the levels of 1 O 2 , OH·, and O 2 -· . More importantly, TPT@B 12 H 12 effectively suppress the melanoma growth both in vitro and in vivo through 1 O 2 , OH·, and O 2 -· generation. This study specifically highlights the great clinical translational potential of TPT@B 12 H 12 as a CDT reagent.