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Enhancing anticancer effects, decreasing risks and solving practical problems facing 3-bromopyruvate in clinical oncology: 10 years of research experience

Authors El Sayed SM

Received 9 April 2018

Accepted for publication 8 June 2018

Published 15 August 2018 Volume 2018:13 Pages 4699—4709

DOI https://doi.org/10.2147/IJN.S170564

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Thomas Webster


Video abstract presented by Salah Mohamed El Sayed.

Views: 149

Salah Mohamed El Sayed1,2

1Department of Clinical Biochemistry and Molecular Medicine, Taibah College of Medicine, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia; 2Department of Medical Biochemistry, Sohag Faculty of Medicine, Sohag University, Sohag, Egypt

Abstract: 3-Bromopyruvate (3BP) is a promising powerful general anticancer agent. Unfortunately, 3BP release faces many practical and biochemical problems in clinical human oncology, for example, 3BP induces burning venous sensation (during intravenous infusion) and rapid inactivation by thiol groups of glutathione and proteins. 3BP exhibits resistance in glutathione-rich tumors without being able to exert selective targeting. 3BP does not cross the blood–brain barrier and cannot treat nervous system tumors. Importantly, 3BP cannot persist in tumor tissues due to the phenomenon of enhanced permeability and retention effect. Here, the author presents the practical solutions for clinical problems facing 3BP use in clinical oncology, based on over 10 years of experience in 3BP research. Crude (unformulated 3BP that is purchased from chemical companies without being formulated in liposomes or other nanocarriers) should not be administered in clinical oncology. Instead, 3BP is better formulated with liposomes, polyethylene glycol (PEG), PEGylated liposomes (stealth liposomes) or perillyl alcohol that are used currently with many chemotherapeutics for treating clinical tumors in cancer patients. Formulating 3BP with targeted liposomes, for example, with folate, transferrin or other ligands, improves tumor targeting. Formulating 3BP with liposomes, PEG, stealth liposomes or perillyl alcohol may improve its pharmacokinetics, hide it from thiols in the circulation, protect it from serum proteins and enzymes, prevent burning sensation, prolong 3BP’s longevity and facilitate crossing the BBB. Formulating 3BP with stealth liposomes protects 3BP from the reticuloendothelial cells. Liposomal 3BP formulations may retain 3BP better inside the relatively large tumor capillary pores (abolish enhanced permeability and retention effect) sparing normal tissues, facilitate new delivery routes for 3BP (eg, topical and intranasal 3BP administration using perillyl alcohol) and improve cancer cytotoxicity. Formulating 3BP may be promising in overcoming many obstacles in clinical oncology.

Keywords: 3-bromopyruvate, 3BP release, PEG formulation, practical problems, liposomes and targeting cancer

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