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Logic-Gated DNA Intelligent Nanorobots for Cellular Lysosome Interference and Enhanced Therapeutics
Qiwei Wang1,2,3, Ruixue Chang2, Xiuping Li2
1Department of Chemistry, Anhui University, 111 Jiulong Road, Hefei, Anhui, 230601, China.
Angewandte Chemie (International Ed. in English)
|January 28, 2025
Summary
This study introduces a logic-gated DNA nanorobot (Gi-DR) that responds to cellular environments for targeted cancer treatment. It delivers therapeutic agents to lysosomes, enhancing cancer cell destruction and anti-tumor efficacy.
Area of Science:
- Biotechnology
- Nanomedicine
- Molecular Engineering
Background:
- DNA nanodevices offer potential for cellular manipulation and disease treatment.
- Sequential response to diverse cellular microenvironments presents a significant challenge for nanodevices.
- Developing intelligent nanorobots for precise cellular targeting is crucial for advanced therapies.
Purpose of the Study:
- To design and develop a logic-gated intelligent DNA nanorobot (Gi-DR) capable of cascade responses to inter- and intra-cellular microenvironments.
- To achieve lysosome-targeted cargo delivery for enhanced subcellular interference and tumor treatment.
- To program the nanorobot's behavior using a YES-AND logic circuit based on environmental cues.
Main Methods:
- Utilized G-quadruplexes to detect high extracellular K+ concentrations characteristic of cancer cells.
- Engineered an aptamer-based DNA machine for transmembrane payload delivery to lysosomes.
- Employed heterodimeric i-motifs that promote nanoassembly in acidic intracellular environments.
- Implemented a YES-AND logic circuit integrating K+ and H+ as environmental inputs to control nanorobot activation.
Main Results:
- Demonstrated controllable formation of DNA nanostrips within living cells.
- Showcased interference with lysosomal function, leading to inhibited cellular proliferation.
- Successfully delivered a therapeutic agent (ligand-drug conjugate) into target cancer cells.
- Observed significantly enhanced cancer cell lethality and in vivo anti-tumor efficacy.
Conclusions:
- The designed logic-gated DNA nanorobot (Gi-DR) effectively responds to specific cellular microenvironments for targeted therapy.
- This nanorobot facilitates lysosome-targeted delivery and subcellular interference, improving therapeutic outcomes.
- The study highlights broad application prospects for logic-gated DNA nanorobots in cellular function modulation and precision disease treatment.
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