An Aptamer‐Nanotrain Assembled from Six‐Letter DNA Delivers Doxorubicin Selectively to Liver Cancer Cells

Expanding the number of nucleotides in DNA increases the information density of functional DNA molecules, creating nanoassemblies that cannot be invaded by natural DNA/RNA in complex biological systems. Here, we show how six‐letter GACTZP DNA contributes this property in two parts of a nanoassembly:...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2020-01, Vol.59 (2), p.663-668
Main Authors: Zhang, Liqin, Wang, Sai, Yang, Zunyi, Hoshika, Shuichi, Xie, Sitao, Li, Jin, Chen, Xigao, Wan, Shuo, Li, Long, Benner, Steven A., Tan, Weihong
Format: Article
Language:English
Subjects:
Antibodies
aptamer
Aptamers
Aptamers, Nucleotide - chemistry
Assembling
Assembly
Biological evolution
Cell culture
Cell Line, Tumor
Deoxyribonucleic acid
DNA
DNA - chemistry
DNA nanotechnology
Doxorubicin
Doxorubicin - pharmacology
Doxorubicin - therapeutic use
drug delivery
Hepatocytes
Humans
Liver
Liver cancer
Liver Neoplasms - drug therapy
Liver Neoplasms - genetics
nanotrain
Nucleotides
Ribonucleic acid
RNA
Selectivity
six-nucleotide DNA
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Summary:Expanding the number of nucleotides in DNA increases the information density of functional DNA molecules, creating nanoassemblies that cannot be invaded by natural DNA/RNA in complex biological systems. Here, we show how six‐letter GACTZP DNA contributes this property in two parts of a nanoassembly: 1) in an aptamer evolved from a six‐letter DNA library to selectively bind liver cancer cells; and 2) in a six‐letter self‐assembling GACTZP nanotrain that carries the drug doxorubicin. The aptamer‐nanotrain assembly, charged with doxorubicin, selectively kills liver cancer cells in culture, as the selectivity of the aptamer binding directs doxorubicin into the aptamer‐targeted cells. The assembly does not kill untransformed cells that the aptamer does not bind. This architecture, built with an expanded genetic alphabet, is reminiscent of antibodies conjugated to drugs, which presumably act by this mechanism as well, but with the antibody replaced by an aptamer. Crazy train: Folded DNA molecules were evolved or designed from a six‐letter DNA library to perform two non‐genetic functions: binding selectively to liver cancer cells and binding the toxic drug doxorubicin. Combined into an aptamer‐nanotrain conjugate (6N‐Apt‐NTr‐Dox), these selectively kill liver cancer cells. This selective drug delivery is reminiscent of antibody–drug conjugates, but without proteins.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201909691