No abstract

Recently, nanomaterials, particularly catalase, have gained considerable attention in enhancing the outcomes of cancer therapy. To ensure the efficacious clinical application of catalase, a balance between its stability and biosafety is required alongside the maintenance of a high catalytic efficiency. Herein, halloysite clay nanotubes (HNTs) and dodecahydro-dodecaborate (closo-[B12H12]2–) with biocompatible properties were ingeniously combined and reduced in situ to obtain silver nanoparticles (AgNPs) and single-atom nanozyme (SAzyme) composites (HNT@B12H12@Ag catalase) with significantly good antitumor effect and biosafety. This novel designed material (HNT@B12H12@Ag) can help avoid the elevated-temperature calcination that is typically employed as it prepares Ag SAzymes alongside AgNPs while maintaining ~ 100% efficiency of Ag utilization via the reducibility and coordination stabilization of closo-[B12H12]2− and HNTs. Moreover, we investigated the catalytic activity and antimelanoma effects of HNT@B12H12@Ag catalase, and the results revealed that it effectively suppressed melanoma growth in vitro and in vivo via toxic reactive oxygen species generated by mediating the catalytic reactions. This study provides a solid foundation for designing NP/SAzymes with promising clinical translation prospects.

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 in tumor microenvironments. However, the systemic toxicity of metal-based CDT agents has limited their clinical use due to harmful side effects and low efficiency. Herein, we generate a novel CDT agent: 2,4,6-tri(4-pyridyl)-1,3,5-triazine (TPT)/ [closo-B12H12]2−(TPT@ B12H12), which is metal-free and may avoid cumulative toxicity during long-term therapy. We investigated the Fenton-like catalytic activity and anti-melanoma effects of the synthesized boron cluster supramolecular framework TPT@B12H12, and the results showed that it could effectively suppress the melanoma growth both in vitro and in vivo through ROS generation. The favorable properties of the TPT@B12H12 system were rationalized by means of quantum chemistry DFT calculations revealing that TPT@B12H12 substantially decreases the activation barrier compared to the effective Fe2+ ion commonly used in Fenton reactions. This study highlights the great clinical translational potential of TPT@B12H12 as a CDT agent, potentially serving as a prelude to the rapid development of metal-free CDT agents.