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G-Quadruplex Linked DNA Guides Selective Transfection into Nucleolin-Overexpressing Cancer Cells

Gene therapy is a promising approach for treating tumors. Conventional approaches of DNA delivery depending on non-viral or viral vectors are unsatisfactory due to the concerns of biosafety and cell-targeting efficiency. The question how to deliver DNA into tumor cells efficiently and selectively is...

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Autores principales: Xiang, Mengxi, Li, Yongkui, Liu, Jia, Shi, Jie, Ge, Yizhi, Peng, Chen, Bin, Yawen, Wang, Zheng, Wang, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9609445/
https://www.ncbi.nlm.nih.gov/pubmed/36297681
http://dx.doi.org/10.3390/pharmaceutics14102247
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author Xiang, Mengxi
Li, Yongkui
Liu, Jia
Shi, Jie
Ge, Yizhi
Peng, Chen
Bin, Yawen
Wang, Zheng
Wang, Lin
author_facet Xiang, Mengxi
Li, Yongkui
Liu, Jia
Shi, Jie
Ge, Yizhi
Peng, Chen
Bin, Yawen
Wang, Zheng
Wang, Lin
author_sort Xiang, Mengxi
collection PubMed
description Gene therapy is a promising approach for treating tumors. Conventional approaches of DNA delivery depending on non-viral or viral vectors are unsatisfactory due to the concerns of biosafety and cell-targeting efficiency. The question how to deliver DNA into tumor cells efficiently and selectively is a major technological problem in tumor gene therapy. Here, we develop a vector-free gene transfer strategy to deliver genes effectively and selectively by taking advantage of targeting nucleolin. Nucleolin, a shuttle protein moving between cell membrane, cytoplasm and nuclei, is overexpressed in tumor cells. It has a natural ligand G-quadruplex (Gq). Gq-linked DNA (Gq-DNA) is likely to be internalized by ligand dependent uptake mechanisms independently of vectors after neutralizing negative charges of cell membrane by targeting nucleolin. This strategy is referred to as Gq-DNA transfection. Benefiting from its high affinity to nucleolin, Gq-DNA can be effectively delivered into nucleolin-positive tumor cells even nuclei. Gq-DNA transfection is characterized by low cytotoxicity, high efficiency, ease of synthesis, high stability in serum, direct access into nuclei, and specific nucleolin-positive tumor cell targeting.
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spelling pubmed-96094452022-10-28 G-Quadruplex Linked DNA Guides Selective Transfection into Nucleolin-Overexpressing Cancer Cells Xiang, Mengxi Li, Yongkui Liu, Jia Shi, Jie Ge, Yizhi Peng, Chen Bin, Yawen Wang, Zheng Wang, Lin Pharmaceutics Article Gene therapy is a promising approach for treating tumors. Conventional approaches of DNA delivery depending on non-viral or viral vectors are unsatisfactory due to the concerns of biosafety and cell-targeting efficiency. The question how to deliver DNA into tumor cells efficiently and selectively is a major technological problem in tumor gene therapy. Here, we develop a vector-free gene transfer strategy to deliver genes effectively and selectively by taking advantage of targeting nucleolin. Nucleolin, a shuttle protein moving between cell membrane, cytoplasm and nuclei, is overexpressed in tumor cells. It has a natural ligand G-quadruplex (Gq). Gq-linked DNA (Gq-DNA) is likely to be internalized by ligand dependent uptake mechanisms independently of vectors after neutralizing negative charges of cell membrane by targeting nucleolin. This strategy is referred to as Gq-DNA transfection. Benefiting from its high affinity to nucleolin, Gq-DNA can be effectively delivered into nucleolin-positive tumor cells even nuclei. Gq-DNA transfection is characterized by low cytotoxicity, high efficiency, ease of synthesis, high stability in serum, direct access into nuclei, and specific nucleolin-positive tumor cell targeting. MDPI 2022-10-21 /pmc/articles/PMC9609445/ /pubmed/36297681 http://dx.doi.org/10.3390/pharmaceutics14102247 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xiang, Mengxi
Li, Yongkui
Liu, Jia
Shi, Jie
Ge, Yizhi
Peng, Chen
Bin, Yawen
Wang, Zheng
Wang, Lin
G-Quadruplex Linked DNA Guides Selective Transfection into Nucleolin-Overexpressing Cancer Cells
title G-Quadruplex Linked DNA Guides Selective Transfection into Nucleolin-Overexpressing Cancer Cells
title_full G-Quadruplex Linked DNA Guides Selective Transfection into Nucleolin-Overexpressing Cancer Cells
title_fullStr G-Quadruplex Linked DNA Guides Selective Transfection into Nucleolin-Overexpressing Cancer Cells
title_full_unstemmed G-Quadruplex Linked DNA Guides Selective Transfection into Nucleolin-Overexpressing Cancer Cells
title_short G-Quadruplex Linked DNA Guides Selective Transfection into Nucleolin-Overexpressing Cancer Cells
title_sort g-quadruplex linked dna guides selective transfection into nucleolin-overexpressing cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9609445/
https://www.ncbi.nlm.nih.gov/pubmed/36297681
http://dx.doi.org/10.3390/pharmaceutics14102247
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