Targeted Therapy of Colon Cancer by Aptamer-Guided Holliday Junctions Loaded with Doxorubicin

Fengjiao Yao, Yacong An, Xundou Li, Zhaoyi Li, Jinhong Duan, Xian-Da Yang Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Xian-Da Yang Email ayangmd@hotmail.comPurpose: Chemotherap...

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Autores principales:	Yao F, An Y, Li X, Li Z, Duan J, Yang XD
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	colon cancer targeted therapy aptamer holliday junction doxorubicin Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b25843eea0cb480682164cb0008a3238
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spelling	oai:doaj.org-article:b25843eea0cb480682164cb0008a32382021-12-02T09:36:26ZTargeted Therapy of Colon Cancer by Aptamer-Guided Holliday Junctions Loaded with Doxorubicin1178-2013https://doaj.org/article/b25843eea0cb480682164cb0008a32382020-03-01T00:00:00Zhttps://www.dovepress.com/targeted-therapy-of-colon-cancer-by-aptamer-guided-holliday-junctions--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Fengjiao Yao, Yacong An, Xundou Li, Zhaoyi Li, Jinhong Duan, Xian-Da Yang Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Xian-Da Yang Email ayangmd@hotmail.comPurpose: Chemotherapy is the primary treatment for advanced colon cancer, but its efficacy is often limited by severe toxicities. Targeted therapy in the form of selectively drug delivery system (SDDS) is an important strategy to reduce adverse effects. Here, we aim to design a novel SDDS with potential for practical application using biocompatible components and scalable production process, for targeted delivery of doxorubicin (Dox) to colon cancer cells.Methods: The SDDS was made of a self-assembled DNA nano-cross (Holliday junction, or HJ) functionalized by four AS1411 aptamers (Apt-HJ) and loaded with Dox.Results: Apt-HJ had an average size of 12.45 nm and a zeta potential of − 11.6 mV. Compared with the monovalent AS1411 aptamer, the quadrivalent Apt-HJ showed stronger binding to target cancer cells (CT26). A complex of Apt-HJ and doxorubicin (Apt-HJ-Dox) was formed by intercalating Dox into the DNA structure of Apt-HJ, with each complex carrying approximately 17 Dox molecules. Confocal microscopy revealed that Apt-HJ-Dox selectively delivered Dox into CT26 colon cancer cells but not the control cells. Moreover, Apt-HJ-Dox achieved targeted killing of CT26 cancer cells in vitro and reduced the damage to control cells. Importantly, compared with free Dox, Apt-HJ-Dox significantly enhanced the antitumor efficacy in vivo without boosting the adverse effects.Conclusion: These results suggest that Apt-HJ-Dox has application potential in targeted treatment of colon cancer.Keywords: colon cancer, targeted therapy, aptamer, holliday junction, doxorubicinYao FAn YLi XLi ZDuan JYang XDDove Medical Pressarticlecolon cancertargeted therapyaptamerholliday junctiondoxorubicinMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 2119-2129 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	colon cancer targeted therapy aptamer holliday junction doxorubicin Medicine (General) R5-920
spellingShingle	colon cancer targeted therapy aptamer holliday junction doxorubicin Medicine (General) R5-920 Yao F An Y Li X Li Z Duan J Yang XD Targeted Therapy of Colon Cancer by Aptamer-Guided Holliday Junctions Loaded with Doxorubicin
description	Fengjiao Yao, Yacong An, Xundou Li, Zhaoyi Li, Jinhong Duan, Xian-Da Yang Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Xian-Da Yang Email ayangmd@hotmail.comPurpose: Chemotherapy is the primary treatment for advanced colon cancer, but its efficacy is often limited by severe toxicities. Targeted therapy in the form of selectively drug delivery system (SDDS) is an important strategy to reduce adverse effects. Here, we aim to design a novel SDDS with potential for practical application using biocompatible components and scalable production process, for targeted delivery of doxorubicin (Dox) to colon cancer cells.Methods: The SDDS was made of a self-assembled DNA nano-cross (Holliday junction, or HJ) functionalized by four AS1411 aptamers (Apt-HJ) and loaded with Dox.Results: Apt-HJ had an average size of 12.45 nm and a zeta potential of − 11.6 mV. Compared with the monovalent AS1411 aptamer, the quadrivalent Apt-HJ showed stronger binding to target cancer cells (CT26). A complex of Apt-HJ and doxorubicin (Apt-HJ-Dox) was formed by intercalating Dox into the DNA structure of Apt-HJ, with each complex carrying approximately 17 Dox molecules. Confocal microscopy revealed that Apt-HJ-Dox selectively delivered Dox into CT26 colon cancer cells but not the control cells. Moreover, Apt-HJ-Dox achieved targeted killing of CT26 cancer cells in vitro and reduced the damage to control cells. Importantly, compared with free Dox, Apt-HJ-Dox significantly enhanced the antitumor efficacy in vivo without boosting the adverse effects.Conclusion: These results suggest that Apt-HJ-Dox has application potential in targeted treatment of colon cancer.Keywords: colon cancer, targeted therapy, aptamer, holliday junction, doxorubicin
format	article
author	Yao F An Y Li X Li Z Duan J Yang XD
author_facet	Yao F An Y Li X Li Z Duan J Yang XD
author_sort	Yao F
title	Targeted Therapy of Colon Cancer by Aptamer-Guided Holliday Junctions Loaded with Doxorubicin
title_short	Targeted Therapy of Colon Cancer by Aptamer-Guided Holliday Junctions Loaded with Doxorubicin
title_full	Targeted Therapy of Colon Cancer by Aptamer-Guided Holliday Junctions Loaded with Doxorubicin
title_fullStr	Targeted Therapy of Colon Cancer by Aptamer-Guided Holliday Junctions Loaded with Doxorubicin
title_full_unstemmed	Targeted Therapy of Colon Cancer by Aptamer-Guided Holliday Junctions Loaded with Doxorubicin
title_sort	targeted therapy of colon cancer by aptamer-guided holliday junctions loaded with doxorubicin
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/b25843eea0cb480682164cb0008a3238
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Targeted Therapy of Colon Cancer by Aptamer-Guided Holliday Junctions Loaded with Doxorubicin

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