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Engineering a Second-Order DNA Logic-Gated Nanorobot to Sense and Release on Live Cell Membranes for Multiplexed Diagnosis and Synergistic Therapy
2024-10-09 43

Affiliations

  • Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan, 410082, China.
  • The Cancer Hospital of the University of, Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China.
  • Institute of Molecular Medicine (IMM), Renji Hospital, Shanghai Jiao Tong University School of Medicine, College of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.

PMID:  33908144 DOI: 10.1002/anie.202103993

Abstract

Background: Tumor biomarker-based theranostics have achieved broad interest and success in recent years. However, single biomarker-based recognition can cause false-positive feedback, including the on-target off-tumor phenomenon, in the absence of tumor-specific antigen. Multibiomarker-based recognition molecules often elicit nonspecific and undesired internalization when they bind to "bystander" cells.

Results: We report a universal DNA tetrahedral scaffold (DTS) that anchors on the cell membrane to load multiple aptamers and therapeutics for precise and effective theranostics. This DNA logic-gated nanorobot (DLGN) facilitates precise discrimination among five cell lines and triggers synergistic killing of effector aptamer-tethered synergistic drugs (EASDs) to target cancer cells.

Conclusion: Logic-gated recognition integrated into aptamer-functionalized molecular machines will promote fast tumor profiling, in situ capture and isolation, and safe delivery of precise medicine.

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