Scholarlink

<p>Therapeutic biosynthesis has emerged as a cutting-edge technology for precision medicine. However, achieving the highly-controlled synthesis of abiotic matter at the tumor location for efficient therapy remains an ongoing challenge. Here, we develop a “dual lock-and-key” system to accomplish tumor cell-specific intracellular synthesis for accurate cancer therapy. The proposed precursor structure (“dual-lock”) can be activated in target cancer cells by two endogenously overexpressed enzymes (“dual key”), azor-eductase (AzoR) and nitroreductase (NTR), to initiate a condensation reaction for the <i>in situ</i> synthesis of fibrous mesh covalent organic polymers (Fm-COPs). The synthesized Fm-COPs demonstrate an excellent ability to disrupt the cytoskeleton, thereby inhibiting cell migration, suppressing cell invasion, and inducing apoptosis. Importantly, by leveraging the dual enzyme-responsive mechanism and small-molecule precursors the proposed intracellular synthesis strategy performs well on specific enrichment and tumor penetration, resulting in effective inhibition of tumor proliferation without side effects. Our findings suggest that this “dual lock-and-key” engineered intracellular synthesis represents a promising next-generation option for high-precision cancer therapies.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A “dual lock-and-key” engineered intracellular synthesis for high-precision cancer therapy

  • 期刊论文

  • 发表日期：

    2026年7月21日

查看全文
  • Hanbin Xu,
  • Mengli Liu,
  • Mengqi Zhao,
  • Mingjie Ye,
  • Yating Gao,
  • Chengye Xi,
  • Yunqing Cao,
  • Junjie Yu,
  • Mahmoud Elsayed Hafez,
  • Ruocan Qian,
  • Binbin Chen,
  • Dawei Li

摘要

Therapeutic biosynthesis has emerged as a cutting-edge technology for precision medicine. However, achieving the highly-controlled synthesis of abiotic matter at the tumor location for efficient therapy remains an ongoing challenge. Here, we develop a “dual lock-and-key” system to accomplish tumor cell-specific intracellular synthesis for accurate cancer therapy. The proposed precursor structure (“dual-lock”) can be activated in target cancer cells by two endogenously overexpressed enzymes (“dual key”), azor-eductase (AzoR) and nitroreductase (NTR), to initiate a condensation reaction for the in situ synthesis of fibrous mesh covalent organic polymers (Fm-COPs). The synthesized Fm-COPs demonstrate an excellent ability to disrupt the cytoskeleton, thereby inhibiting cell migration, suppressing cell invasion, and inducing apoptosis. Importantly, by leveraging the dual enzyme-responsive mechanism and small-molecule precursors the proposed intracellular synthesis strategy performs well on specific enrichment and tumor penetration, resulting in effective inhibition of tumor proliferation without side effects. Our findings suggest that this “dual lock-and-key” engineered intracellular synthesis represents a promising next-generation option for high-precision cancer therapies.