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<p>The endoplasmic reticulum (ER) serves as a critical target for diverse therapeutics. Developing novel ER delivery strategies is essential for enhancing drug efficacy. Current efforts focus on tissue and cellular-level drug delivery, while subcellular-targeting remains confined to lysosomal escape into the cytosol. Although approaches employing STING agonists, E3 viral peptides as targeting ligands have been explored, the “last-mile” delivery from cytosol to ER persists as a challenge due to unclear mechanisms and low efficiency. We employ the ribosome as a drug carrier to exploit its trafficking mechanism toward the ER during translation, enabling efficient delivery of drugs. We used levofloxacin as a ribosome lead molecule and synthesized Lc-RCy by coupling it with RGD and cyanine dye (Cy). Lc-RCy effectively binds ribosomes and reaches the ER during protein translation. Subsequent photodynamic treatment near the ER using the photodynamic effect of Cy induced significant immunogenic cell death and inhibited tumor growth.</p>

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Employing ribosome as endoplasmic reticulum delivery carrier for enhanced tumor immunotherapy

  • 期刊论文

  • 发表日期：

    2026年4月8日

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  • Yong Li,
  • Sui Zhou,
  • Kai Cheng,
  • Li-Li Chen,
  • Chi Zhang,
  • Jia-Hua Zou,
  • Bo Liu,
  • Jin-Xuan Fan,
  • Yuan-Di Zhao,
  • Xiao-Shuai Zhang

摘要

The endoplasmic reticulum (ER) serves as a critical target for diverse therapeutics. Developing novel ER delivery strategies is essential for enhancing drug efficacy. Current efforts focus on tissue and cellular-level drug delivery, while subcellular-targeting remains confined to lysosomal escape into the cytosol. Although approaches employing STING agonists, E3 viral peptides as targeting ligands have been explored, the “last-mile” delivery from cytosol to ER persists as a challenge due to unclear mechanisms and low efficiency. We employ the ribosome as a drug carrier to exploit its trafficking mechanism toward the ER during translation, enabling efficient delivery of drugs. We used levofloxacin as a ribosome lead molecule and synthesized Lc-RCy by coupling it with RGD and cyanine dye (Cy). Lc-RCy effectively binds ribosomes and reaches the ER during protein translation. Subsequent photodynamic treatment near the ER using the photodynamic effect of Cy induced significant immunogenic cell death and inhibited tumor growth.