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<p>The integration of molecular computation with nanomedicine holds transformative potential for precision cancer theranostics. However, achieving an intelligent, multi-input decision-making process within living cells remains a formidable challenge because of the complexity of intracellular signaling networks. Here, we present a set of DNA tetrahedron logic processors that enable smart intracellular computing through a programmable three-input architecture capable of executing seven Boolean operations—OR, AND, NOR, NAND, XOR, majority (MAJ), and OR-AND—in response to endogenous miRNA signals. Building upon the cell-internalizable tetrahedral framework nucleic acid, this processor functions as an autonomous sense-and-treat module: it decodes combinatorial biomarker states and conditionally releases therapeutic siRNA only when a predefined logical condition is met. As a proof of concept, in precision oncology, we engineered a MAJ-gated nanoplatform (siR@MAJ) that selectively silences survivin in MCF-7 breast cancer cells that exhibit a specific tri-miRNA signature while sparing other cell types. This approach has achieved potent tumor suppression both in vitro and in vivo with high specificity and minimal off-target effects. By integrating multi-target detection into a single logic circuit, this processor significantly improves the discriminative capability within complex biological environments. Our work establishes a foundational platform for intelligent intracellular diagnostics and therapy, paving the way toward adaptive, logic-driven nanomedicine.</p>

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Intracellular logic computing with DNA tetrahedron processors enables precision cancer theranostics

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月2日

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  • Yang Gao,
  • Yun Wang,
  • Yunlong Qin,
  • Geru Zhang,
  • Shaojingya Gao,
  • Wen Chen,
  • Siyi Yang,
  • Xiao Yang,
  • Yuanlin Tang,
  • Yao He,
  • Yunfeng Lin,
  • Itamar Willner,
  • Taoran Tian,
  • Xiaoxiao Cai

摘要

The integration of molecular computation with nanomedicine holds transformative potential for precision cancer theranostics. However, achieving an intelligent, multi-input decision-making process within living cells remains a formidable challenge because of the complexity of intracellular signaling networks. Here, we present a set of DNA tetrahedron logic processors that enable smart intracellular computing through a programmable three-input architecture capable of executing seven Boolean operations—OR, AND, NOR, NAND, XOR, majority (MAJ), and OR-AND—in response to endogenous miRNA signals. Building upon the cell-internalizable tetrahedral framework nucleic acid, this processor functions as an autonomous sense-and-treat module: it decodes combinatorial biomarker states and conditionally releases therapeutic siRNA only when a predefined logical condition is met. As a proof of concept, in precision oncology, we engineered a MAJ-gated nanoplatform (siR@MAJ) that selectively silences survivin in MCF-7 breast cancer cells that exhibit a specific tri-miRNA signature while sparing other cell types. This approach has achieved potent tumor suppression both in vitro and in vivo with high specificity and minimal off-target effects. By integrating multi-target detection into a single logic circuit, this processor significantly improves the discriminative capability within complex biological environments. Our work establishes a foundational platform for intelligent intracellular diagnostics and therapy, paving the way toward adaptive, logic-driven nanomedicine.