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N-(3-hydroxymethyl-β-carboline-1-yl-ethyl-2-yl)-L-Phe: development toward a nanoscaled antitumor drug capable of treating complicated thrombosis and inflammation

Authors Wu JH, Zhao M, Wang YJ, Wang YN, Zhu HM, Zhao SR, Gui L, Zhang XY, Peng SQ

Received 5 October 2016

Accepted for publication 10 November 2016

Published 17 January 2017 Volume 2017:11 Pages 225—239


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Salvatore Bongarzone

Peer reviewer comments 2

Editor who approved publication: Dr Anastasios Lymperopoulos

Jianhui Wu,1–4 Ming Zhao,1–5 Yuji Wang,1–4 Yaonan Wang,1–4 Haimei Zhu,1–4 Shurui Zhao,1–4 Lin Gui,1–4 Xiaoyi Zhang,1–4 Shiqi Peng1–4

1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, 2Engineering Research Center of Endogenous Prophylactic, Ministry of Education of China, 3Beijing Laboratory of Biomedical Materials, 4College of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 5Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China

Abstract: It is well documented that the surfaces of cancer cells, activated platelets and inflammatory cells are rich in P-selectin. N-(3-hydroxymethyl-β-carboline-1-yl-ethyl-2-yl)-l-Phe (HMCEF) is a P-selectin inhibitor capable of simultaneously inhibiting thrombosis and inflammation. Based on the knowledge that P-selectin is a common target for antithrombotic, anti-inflammatory and antitumor drugs, the aim of this study article was to estimate the possibility of HMCEF as a nanoscaled antitumor drug. Images of transmission electron micro­scopy, scanning electron microscopy and atomic force microscopy proved that HMCEF forms nanoparticles with a diameter of <120 nm that promote delivery in blood circulation. In vitro HMCEF intercalates into calf thymus DNA, cuts off DNA pBR22 and inhibits the proliferation of cancer cells. In vivo HMCEF dose dependently (0.2, 2 and 200 nmol/kg per day) slows tumor growth in treated S180 mice, and has a minimal effective dose of 2 nmol/kg per day. At 200 nmol/kg per day, HMCEF does not affect the liver and the kidney of the treated S180 mice, and at 20,000 nmol/kg HMCEF does not affect the liver and the kidney of the treated healthy ICR mice. HMCEF is a promising antitumor drug, which is characterized by its high safety and efficacy in the prevention of the complications of thrombosis and inflammation in patients.

Keywords: P-selectin, antitumor, antithrombosis, anti-inflammation, nanomedicine

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