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

Abstract

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-B₁₂ H₁₂ ]^2- (TPT@ B₁₂ H₁₂ ) is reported. Compared to the traditional metal-based CDT agents, TPT@B₁₂ H₁₂ is free of metal avoiding cumulative toxicity during long-term therapy. Density functional theory (DFT) calculation revealed that TPT@B₁₂ H₁₂ 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 [B₁₂ H₁₂ ]^-· and [TPT-H]²⁺ have the capacity to decompose hydrogen into ¹ O₂ , OH·, and O₂ ^-· . With electron paramagnetic resonance and fluorescent probes, it is confirmed that TPT@B₁₂ H₁₂ increases the levels of ¹ O₂ , OH·, and O₂ ^-· . More importantly, TPT@B₁₂ H₁₂ effectively suppress the melanoma growth both in vitro and in vivo through ¹ O₂ , OH·, and O₂ ^-· generation. This study specifically highlights the great clinical translational potential of TPT@B₁₂ H₁₂ as a CDT reagent.

Keywords: boron cluster supramolecular frameworks; chemodynamic therapy; fenton-like catalytic activity; melanoma.