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Crafting Immune-Cancer Cell Crosstalk via Modular Multilayer Logic DNA Nanoadaptors.

Yihan Wang1, Qianying Zhang1, Zejing Xing1

  • 1State Key Laboratory of Analytical Chemistry for Life Science, Chemistry and Biomedicine Innovation Center, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, P.R. China.

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|October 6, 2025
PubMed
Summary

We developed a DNA nanoadaptor (Magic-NA) for programmable control of immune-cancer cell interactions. This tool enables logic-based targeting of cancer cells by natural killer (NK) cells, enhancing precision immunotherapy.

Keywords:
Cell recognitionCell‐cell interactionsDNA structuresLogic operationModular design

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Area of Science:

  • Biotechnology
  • Nanotechnology
  • Immunology

Background:

  • Engineering logic circuits for cell-cell communication is challenging.
  • Synthetic molecular tools can reconfigure cell interactions.
  • Controlling intercellular communication in complex microenvironments requires advanced strategies.

Purpose of the Study:

  • To present a multilayer logic DNA nanoadaptor (Magic-NA) for defining immune-cancer cell crosstalk.
  • To enable customized logic operations integrating cell surface antigens and microenvironmental factors.
  • To advance precision cancer immunotherapy through programmable manipulation of cellular interactions.

Main Methods:

  • Designed a modular Magic-NA with a DNA di-tetrahedral scaffold and plug-and-play logic connectors.
  • Programmed logic circuits and inputs activated by molecular triggers and cell-specific antigens.
  • Demonstrated AND-AND and OR-AND logic gate systems for targeted cell killing.

Main Results:

  • Magic-NA successfully guided natural killer (NK) cells to target cancer cells via AND-AND logic.
  • Targeting was based on tumor microenvironment (TME) acidic pH and cancer antigens PTK7 and MUC1.
  • An OR-AND logic gate system achieved on-demand cell targeting and broad-spectrum cell killing.

Conclusions:

  • Magic-NA provides a programmable platform for Boolean integration of cellular markers and microenvironmental cues.
  • This nanoplatform advances the development of precision cancer immunotherapy by controlling cell-cell interactions.
  • The study offers a new paradigm for manipulating cellular crosstalk in heterogeneous environments.