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<p>A multi pathway enhanced radiotherapeutic strategy is presented that combines PtPd nanozyme-based reactive oxygen species (ROS) amassment with the inhibition of glutathione (GSH) synthesis mediated by L-buthionine sulfoximine (BSO). To this end a&#xa0;(BSO)-loaded biomimetic PtPd nanozyme system (named CPB) coated with cancer cell membrane (CM) was developed for radiotherapy (RT) sensitization and immunogenic cell death (ICD). The CM guides nanoparticles to specifically bind tumor cells via homologous targeting, and serves as an efficient carrier for BSO, preventing leakage in blood circulation and enabling precise BSO release in tumors. Then, BSO block both the substrate and enzymatic pathways critical for GSH production by inhibiting glutamylcysteine synthetase (γ-GCS). PtPd nanozyme could amplify oxidative stress in tumor microenvironment (TME) by catalyzing hydrogen peroxide to produce hydroxyl radical (<b>·</b>OH). Furthermore, the presence of Pt and Pd in CPB can enhance local RT energy deposition in tumor site. Both in vitro and in vivo experiments showed CPB significantly inhibiting tumor growth with good biocompatibility. This study underscores that robust RT sensitization is attainable by means of inhibiting γ-GCS synthesis while boosting the production of ROS.</p> Graphical Abstract <p></p>

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Biomimetic PtPd nanozyme induce glutamylcysteine synthetase inhibition for enhanced radioimmunotherapy

  • 期刊论文

  • 发表日期：

    2026年4月9日

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  • Huangang Jiang,
  • Hongyang Wu,
  • Tengfei Wang,
  • Dazhen Jiang,
  • Tumaresi Ainiwaer,
  • Yufeng Gu,
  • Lingze Hu,
  • Shuokan Ma,
  • Gaili Chen

摘要

A multi pathway enhanced radiotherapeutic strategy is presented that combines PtPd nanozyme-based reactive oxygen species (ROS) amassment with the inhibition of glutathione (GSH) synthesis mediated by L-buthionine sulfoximine (BSO). To this end a (BSO)-loaded biomimetic PtPd nanozyme system (named CPB) coated with cancer cell membrane (CM) was developed for radiotherapy (RT) sensitization and immunogenic cell death (ICD). The CM guides nanoparticles to specifically bind tumor cells via homologous targeting, and serves as an efficient carrier for BSO, preventing leakage in blood circulation and enabling precise BSO release in tumors. Then, BSO block both the substrate and enzymatic pathways critical for GSH production by inhibiting glutamylcysteine synthetase (γ-GCS). PtPd nanozyme could amplify oxidative stress in tumor microenvironment (TME) by catalyzing hydrogen peroxide to produce hydroxyl radical (·OH). Furthermore, the presence of Pt and Pd in CPB can enhance local RT energy deposition in tumor site. Both in vitro and in vivo experiments showed CPB significantly inhibiting tumor growth with good biocompatibility. This study underscores that robust RT sensitization is attainable by means of inhibiting γ-GCS synthesis while boosting the production of ROS.

Graphical Abstract