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核心技术专利:CN118964589B侵权必究
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A DNA robotic switch with regulated autonomous display of cytotoxic ligand nanopatterns.

作者信息

Wang Yang, Baars Igor, Berzina Ieva, Rocamonde-Lago Iris, Shen Boxuan, Yang Yunshi, Lolaico Marco, Waldvogel Janine, Smyrlaki Ioanna, Zhu Keying, Harris Robert A, Högberg Björn

机构信息

Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

Biohybrid Materials, Department of Bioproducts and Biosystems, Aalto University School of Chemical Engineering, Aalto, Finland.

出版信息

Nat Nanotechnol. 2024 Sep;19(9):1366-1374. doi: 10.1038/s41565-024-01676-4. Epub 2024 Jul 1.


DOI:10.1038/s41565-024-01676-4
PMID:38951595
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11405282/
Abstract

The clustering of death receptors (DRs) at the membrane leads to apoptosis. With the goal of treating tumours, multivalent molecular tools that initiate this mechanism have been developed. However, DRs are also ubiquitously expressed in healthy tissue. Here we present a stimuli-responsive robotic switch nanodevice that can autonomously and selectively turn on the display of cytotoxic ligand patterns in tumour microenvironments. We demonstrate a switchable DNA origami that normally hides six ligands but displays them as a hexagonal pattern 10 nm in diameter once under higher acidity. This can effectively cluster DRs and trigger apoptosis of human breast cancer cells at pH 6.5 while remaining inert at pH 7.4. When administered to mice bearing human breast cancer xenografts, this nanodevice decreased tumour growth by up to 70%. The data demonstrate the feasibility and opportunities for developing ligand pattern switches as a path for targeted treatment.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d43/11405282/13d521d6122c/41565_2024_1676_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d43/11405282/caec63c821af/41565_2024_1676_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d43/11405282/9c91ea5f11da/41565_2024_1676_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d43/11405282/3c47c9c95754/41565_2024_1676_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d43/11405282/4220671ea573/41565_2024_1676_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d43/11405282/b364ead108e1/41565_2024_1676_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d43/11405282/13d521d6122c/41565_2024_1676_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d43/11405282/caec63c821af/41565_2024_1676_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d43/11405282/9c91ea5f11da/41565_2024_1676_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d43/11405282/3c47c9c95754/41565_2024_1676_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d43/11405282/4220671ea573/41565_2024_1676_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d43/11405282/b364ead108e1/41565_2024_1676_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d43/11405282/13d521d6122c/41565_2024_1676_Fig6_HTML.jpg

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引用本文的文献

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[2]
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[3]
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[4]
Effects of DNA Origami-Based Nanoagent Design on Apoptosis Induction in a Large 3D Cancer Spheroid Model.

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[5]
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[6]
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[7]
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[8]
Nanocarrier imaging at single-cell resolution across entire mouse bodies with deep learning.

Nat Biotechnol. 2025-1-14

本文引用的文献

[1]
Folding Double-Stranded DNA into Designed Shapes with Triplex-Forming Oligonucleotides.

Adv Mater. 2023-10

[2]
Reconfigurable pH-Responsive DNA Origami Lattices.

ACS Nano. 2023-6-13

[3]
Functionalizing DNA origami to investigate and interact with biological systems.

Nat Rev Mater. 2023-2

[4]
3DFlex: determining structure and motion of flexible proteins from cryo-EM.

Nat Methods. 2023-6

[5]
Triple-Stranded DNA As a Structural Element in DNA Origami.

ACS Nano. 2023-5-23

[6]
Nanoscale Organization of TRAIL Trimers using DNA Origami to Promote Clustering of Death Receptor and Cancer Cell Apoptosis.

Small. 2023-6

[7]
Non-viral precision T cell receptor replacement for personalized cell therapy.

Nature. 2023-3

[8]
On-demand targeting nanotheranostics with stimuli-responsive releasing property to improve delivery efficiency to cancer.

Biomaterials. 2022-11

[9]
Design and simulation of DNA, RNA and hybrid protein-nucleic acid nanostructures with oxView.

Nat Protoc. 2022-8

[10]
Double- to Single-Strand Transition Induces Forces and Motion in DNA Origami Nanostructures.

Adv Mater. 2021-9

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