Microfluidic Synthesis of CuH Nanoparticles for Antitumor Therapy through Hydrogen-Enhanced Apoptosis and Cuproptosis.

Abstract

Cuproptosis has drawn enormous attention in antitumor material fields; however, the responsive activation of cuproptosis against tumors using nanomaterials with high atom utilization is still challenging. Herein, a copper-based nanoplatform consisting of acid-degradable copper hydride (CuH) nanoparticles was developed via a microfluidic synthesis. After coating with tumor-targeting hyaluronic acid (HA), the nanoplatform denoted as HA-CuH-PVP (HCP) shows conspicuous damage toward tumor cells by generating Cu⁺ and hydrogen (H₂) simultaneously. Cu⁺ can induce apoptosis by relying on Fenton-like reactions and lead to cuproptosis by causing mitochondrial protein aggregation. Besides, the existence of H₂ can enhance both cell death types by causing mitochondrial dysfunction and intracellular redox homeostatic disorders. <i>In vivo</i> experimental results further exhibit the desirable potential of HCP for killing tumor cells and inhibiting lung metastases, which will broaden the horizons of designing copper-based materials triggering apoptosis and cuproptosis for better antitumor efficacy.