Hemorrhage in mouse tumors induced by dodecaborate cluster lipids intended for boron neutron capture therapy

Tanja Schaffran,1 Nan Jiang,1 Markus Bergmann,2,3 Ekkehard Küstermann,4 Regine Süss,5 Rolf Schubert,5 Franz M Wagner,6 Doaa Awad,7 Detlef Gabel1,2,8 1Department of Chemistry, University of Bremen, 2Institute of Neuropathology, Klinikum Bremen-Mitte; 3Cooperative Center Medicine,...

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Autores principales: Schaffran T, Jiang N, Bergmann M, Küstermann E, Süss R, Schubert R, Wagner FM, Awad D, Gabel D
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Publicado: Dove Medical Press 2014
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spelling oai:doaj.org-article:6ec7216d2d9643579188f8c26e9effea2021-12-02T02:31:41ZHemorrhage in mouse tumors induced by dodecaborate cluster lipids intended for boron neutron capture therapy1178-2013https://doaj.org/article/6ec7216d2d9643579188f8c26e9effea2014-07-01T00:00:00Zhttp://www.dovepress.com/hemorrhage-in-mouse-tumors-induced-by-dodecaborate-cluster-lipids-inte-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Tanja Schaffran,1 Nan Jiang,1 Markus Bergmann,2,3 Ekkehard Küstermann,4 Regine Süss,5 Rolf Schubert,5 Franz M Wagner,6 Doaa Awad,7 Detlef Gabel1,2,8 1Department of Chemistry, University of Bremen, 2Institute of Neuropathology, Klinikum Bremen-Mitte; 3Cooperative Center Medicine, University of Bremen, 4“In-vivo-MR” AG, FB2, University of Bremen, Bremen, 5Pharmaceutical Technology, University of Freiburg, Freiburg im Breisgau, 6Forschungsneutronenquelle Heinz Maier-Leibnitz (FRM II), Technische Unversitaet Muenchen, Garching, Germany; 7Department of Biochemistry, Alexandria University, Alexandria, Egypt; 8School of Engineering and Science, Jacobs University Bremen, Bremen, Germany Abstract: The potential of boron-containing lipids with three different structures, which were intended for use in boron neutron capture therapy, was investigated. All three types of boron lipids contained the anionic dodecaborate cluster as the headgroup. Their effects on two different tumor models in mice following intravenous injection were tested; for this, liposomes with boron lipid, distearoyl phosphatidylcholine, and cholesterol as helper lipids, and containing a polyethylene glycol lipid for steric protection, were administered intravenously into tumor-bearing mice (C3H mice for SCCVII squamous cell carcinoma and BALB/c mice for CT26/WT colon carcinoma). With the exception of one lipid (B-THF-14), the lipids were well tolerated, and no other animal was lost due to systemic toxicity. The lipid which led to death was not found to be much more toxic in cell culture than the other boron lipids. All of the lipids that were well tolerated showed hemorrhage in both tumor models within a few hours after administration. The hemorrhage could be seen by in vivo magnetic resonance and histology, and was found to occur within a few hours. The degree of hemorrhage depended on the amount of boron administered and on the tumor model. The observed unwanted effect of the lipids precludes their use in boron neutron capture therapy. Keywords: liposomes, histology, magnetic resonance imaging, pharmacodynamicsSchaffran TJiang NBergmann MKüstermann ESüss RSchubert RWagner FMAwad DGabel DDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 3583-3590 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Schaffran T
Jiang N
Bergmann M
Küstermann E
Süss R
Schubert R
Wagner FM
Awad D
Gabel D
Hemorrhage in mouse tumors induced by dodecaborate cluster lipids intended for boron neutron capture therapy
description Tanja Schaffran,1 Nan Jiang,1 Markus Bergmann,2,3 Ekkehard Küstermann,4 Regine Süss,5 Rolf Schubert,5 Franz M Wagner,6 Doaa Awad,7 Detlef Gabel1,2,8 1Department of Chemistry, University of Bremen, 2Institute of Neuropathology, Klinikum Bremen-Mitte; 3Cooperative Center Medicine, University of Bremen, 4“In-vivo-MR” AG, FB2, University of Bremen, Bremen, 5Pharmaceutical Technology, University of Freiburg, Freiburg im Breisgau, 6Forschungsneutronenquelle Heinz Maier-Leibnitz (FRM II), Technische Unversitaet Muenchen, Garching, Germany; 7Department of Biochemistry, Alexandria University, Alexandria, Egypt; 8School of Engineering and Science, Jacobs University Bremen, Bremen, Germany Abstract: The potential of boron-containing lipids with three different structures, which were intended for use in boron neutron capture therapy, was investigated. All three types of boron lipids contained the anionic dodecaborate cluster as the headgroup. Their effects on two different tumor models in mice following intravenous injection were tested; for this, liposomes with boron lipid, distearoyl phosphatidylcholine, and cholesterol as helper lipids, and containing a polyethylene glycol lipid for steric protection, were administered intravenously into tumor-bearing mice (C3H mice for SCCVII squamous cell carcinoma and BALB/c mice for CT26/WT colon carcinoma). With the exception of one lipid (B-THF-14), the lipids were well tolerated, and no other animal was lost due to systemic toxicity. The lipid which led to death was not found to be much more toxic in cell culture than the other boron lipids. All of the lipids that were well tolerated showed hemorrhage in both tumor models within a few hours after administration. The hemorrhage could be seen by in vivo magnetic resonance and histology, and was found to occur within a few hours. The degree of hemorrhage depended on the amount of boron administered and on the tumor model. The observed unwanted effect of the lipids precludes their use in boron neutron capture therapy. Keywords: liposomes, histology, magnetic resonance imaging, pharmacodynamics
format article
author Schaffran T
Jiang N
Bergmann M
Küstermann E
Süss R
Schubert R
Wagner FM
Awad D
Gabel D
author_facet Schaffran T
Jiang N
Bergmann M
Küstermann E
Süss R
Schubert R
Wagner FM
Awad D
Gabel D
author_sort Schaffran T
title Hemorrhage in mouse tumors induced by dodecaborate cluster lipids intended for boron neutron capture therapy
title_short Hemorrhage in mouse tumors induced by dodecaborate cluster lipids intended for boron neutron capture therapy
title_full Hemorrhage in mouse tumors induced by dodecaborate cluster lipids intended for boron neutron capture therapy
title_fullStr Hemorrhage in mouse tumors induced by dodecaborate cluster lipids intended for boron neutron capture therapy
title_full_unstemmed Hemorrhage in mouse tumors induced by dodecaborate cluster lipids intended for boron neutron capture therapy
title_sort hemorrhage in mouse tumors induced by dodecaborate cluster lipids intended for boron neutron capture therapy
publisher Dove Medical Press
publishDate 2014
url https://doaj.org/article/6ec7216d2d9643579188f8c26e9effea
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