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<p>DNA-based molecular computation enables targeting of cells via multiple surface receptors. However, existing platforms are often limited to single-receptor detection per operation or rely on freely diffusing components, a common source of off-target interference. Here we show an intelligent DNA nanodevice (DND) that integrates multivalent recognition, logic‑gated computation, and spatially precise drug delivery in a single nanostructure. The DND comprises a doxorubicin-loaded tetrahedral DNA framework (tFNA@Dox) connected via three allosteric aptamer arms to a cholesterol-modified membrane anchor. Simultaneous binding of all three aptamers triggers an AND‑logic gate, releasing tFNA@Dox specifically at the target cell membrane. This localized sense‑and‑act mechanism maximizes therapeutic specificity and minimizes systemic exposure. In tumor-bearing mice, DND@Dox effectively accumulated in tumors, significantly inhibited tumor growth under local and systemic administration, and reduced systemic toxicity. This work establishes a versatile platform for logic‑controlled, multimarker‑guided cancer theranostics.</p>

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Membrane-anchored DNA nanodevice with allosteric aptamer arms enables parallel probing and on-site drug delivery

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月7日

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  • Meiqin Zhang,
  • Yinghao Cheng,
  • Nan Chen,
  • Wenbin Huang,
  • Linwen Lan,
  • Yi Yuan,
  • Jiangchuan Du,
  • Linjun Zhang,
  • Xuefen Chen,
  • Zhifa Shen,
  • Chang Xue

摘要

DNA-based molecular computation enables targeting of cells via multiple surface receptors. However, existing platforms are often limited to single-receptor detection per operation or rely on freely diffusing components, a common source of off-target interference. Here we show an intelligent DNA nanodevice (DND) that integrates multivalent recognition, logic‑gated computation, and spatially precise drug delivery in a single nanostructure. The DND comprises a doxorubicin-loaded tetrahedral DNA framework (tFNA@Dox) connected via three allosteric aptamer arms to a cholesterol-modified membrane anchor. Simultaneous binding of all three aptamers triggers an AND‑logic gate, releasing tFNA@Dox specifically at the target cell membrane. This localized sense‑and‑act mechanism maximizes therapeutic specificity and minimizes systemic exposure. In tumor-bearing mice, DND@Dox effectively accumulated in tumors, significantly inhibited tumor growth under local and systemic administration, and reduced systemic toxicity. This work establishes a versatile platform for logic‑controlled, multimarker‑guided cancer theranostics.