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

Authors Yao F, An Y, Li X, Li Z, Duan J, Yang XD

Received 26 November 2019

Accepted for publication 10 March 2020

Published 27 March 2020 Volume 2020:15 Pages 2119—2129

DOI https://doi.org/10.2147/IJN.S240083

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Yan Shen


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 China

Correspondence: Xian-Da Yang Email ayangmd@hotmail.com

Purpose: 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

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