Back to Journals » International Journal of Nanomedicine » Volume 12

ATIQCTPC: a nanomedicine capable of targeting tumor and blocking thrombosis in vivo

Authors Xu X, Wang Y, Wu J, Hu X, Zhu H, Zhang X, Wang YN, Gui L, Zhao M, Peng S

Received 11 December 2016

Accepted for publication 1 February 2017

Published 13 June 2017 Volume 2017:12 Pages 4415—4431

DOI https://doi.org/10.2147/IJN.S129989

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Linlin Sun


Xinyi Xu,1 Yuji Wang,1 Jianhui Wu,1 Xi Hu,1 Haimei Zhu,1 Xiaoyi Zhang,1 Yaonan Wang,1 Lin Gui,1 Ming Zhao,1,2 Shiqi Peng1

1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China


Abstract: To overcome the harmful side effects, low tolerance, and undesirable outcomes of the anticancer drugs, we used ethane-1,2-diamine to bridge antitumoral (S)-3-acetyl-4-oxo-tetrahydroindolo[2,3-a]quinolizine-6-carboxylic acid (ATIQC) and tumor-targeting d-glucuronic acid, thereby providing (6S)-3-acetyl-4-oxo-N-(2-(3,4,5,6-tetrahydroxytetrahydro-2H-pyran-2-carboxamido)ethyl)-4,6,7,12-tetrahydroindolo[2,3-a]quinolizine-6-carboxamide (ATIQCTPC). Atomic force microscopy images visualized, that in serum, ATIQCTPC formed particles of height <81 nm. These particles effectively avoided phagocytosis of macrophages and were stable in blood circulation. Distribution analysis indicated that ATIQCTPC accumulated and released ATIQC in the tumor tissue through a targeting manner. Thus, the antitumor and the anti-thrombotic activities of ATIQCTPC were 100-fold higher than those of ATIQC, and ATIQCTPC was able to prevent cancer patients from suffering from thrombosis. Based on the observation that ATIQCTPC decreased serum tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) in S180 mice, we hypothesized that this is the mechanism that ATIQCTPC utilized to slow tumor growth. Additionally, we observed that ATIQCTPC inhibited thrombosis by decreasing serum P-selectin of thrombotic rats. The intermolecular association and the hexamerization manner of ATIQCTPC were experimentally evidenced and correlated with the formation of the nanoparticles.

Keywords: tumor, thrombosis, targeting, nanoparticle, TNF-α, IL-8, P-selectin

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]