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

Abstract

AbstractChemodynamic 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‐B12H12]2−(TPT@ B12H12) is reported. Compared to the traditional metal‐based CDT agents, TPT@B12H12 is free of metal avoiding cumulative toxicity during long‐term therapy. Density functional theory (DFT) calculation revealed that TPT@B12H12 decreased the activation barrier more than 3.5 times being a more effective catalyst than the Fe2+ ion (the Fenton reaction), which decreases the barrier about twice. Mechanismly, the theory calculation indicated that both [B12H12]−· and [TPT‐H]2+ have the capacity to decompose hydrogen into 1O2, OH·, and O2−·. With electron paramagnetic resonance and fluorescent probes, it is confirmed that TPT@B12H12 increases the levels of 1O2, OH·, and O2−·. More importantly, TPT@B12H12 effectively suppress the melanoma growth both in vitro and in vivo through 1O2, OH·, and O2−· generation. This study specifically highlights the great clinical translational potential of TPT@B12H12 as a CDT reagent.