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An Aptamer-Nanotrain Assembled from Six-Letter DNA Delivers Doxorubicin Selectively to Liver Cancer Cells |
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| Authors: | Dr Liqin Zhang Prof?Dr Sai Wang Dr Zunyi Yang Dr Shuichi Hoshika Sitao Xie Jin Li Dr Xigao Chen Dr Shuo Wan Dr Long Li Prof?Dr Steven A Benner Prof?Dr Weihong Tan |
| Institution: | 1. 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
Department of Chemistry, Department of Physiology and Functional Genomics, UF Health Cancer Center, UF Genetics Institute, University of Florida, Gainesville, FL, 32611 USA These authors contributed equally to this work.;2. Department of Chemistry, Department of Physiology and Functional Genomics, UF Health Cancer Center, UF Genetics Institute, University of Florida, Gainesville, FL, 32611 USA Current address: College of Food Science and Engineering, Ocean University of China, Qingdao, Shandong, 266003 China These authors contributed equally to this work.;3. Foundation for Applied Molecular Evolution, 13709 Progress Boulevard, Box 7, Alachua, FL, 32615 USA Firebird Biomolecular Sciences LLC, 13709 Progress Boulevard, Box 17, Alachua, FL, 32615 USA These authors contributed equally to this work.;4. Foundation for Applied Molecular Evolution, 13709 Progress Boulevard, Box 7, Alachua, FL, 32615 USA Firebird Biomolecular Sciences LLC, 13709 Progress Boulevard, Box 17, Alachua, FL, 32615 USA;5. 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;6. Department of Chemistry, Department of Physiology and Functional Genomics, UF Health Cancer Center, UF Genetics Institute, University of Florida, Gainesville, FL, 32611 USA;7. Foundation for Applied Molecular Evolution, 13709 Progress Boulevard, Box 7, Alachua, FL, 32615 USA |
| Abstract: | 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. |
| Keywords: | Aptamer DNA-Nanotechnologie Wirkstofftransport Nanotrains Sechs-Nukleotid-DNA |