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 H ] (TPT@ B H ) is reported. Compared to the traditional metal-based CDT agents, TPT@B H is free of metal avoiding cumulative toxicity during long-term therapy. Density functional theory (DFT) calculation revealed that TPT@B H decreased the activation barrier more than 3.5 times being a more effective catalyst than the Fe ion (the Fenton reaction), which decreases the barrier about twice. Mechanismly, the theory calculation indicated that both [B H ] and [TPT-H] have the capacity to decompose hydrogen into O , OH·, and O . With electron paramagnetic resonance and fluorescent probes, it is confirmed that TPT@B H increases the levels of O , OH·, and O . More importantly, TPT@B H effectively suppress the melanoma growth both in vitro and in vivo through O , OH·, and O generation. This study specifically highlights the great clinical translational potential of TPT@B H as a CDT reagent.