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Boron neutron capture therapy assisted by boron-conjugated nanoparticles

Boron neutron capture therapy assisted by boron-conjugated nanoparticles For high-performance boron neutron capture therapy (BNCT), core-shell-type biodegradable nanoparticles possessing boron clusters in their cores are designed to improve their accumulation tendency in the tumor region. The copolymerization of styrene carrying carborane with a poly(ethylene glycol)-block-poly(lactide) copolymer (PEG-b-PLA) that possesses an acetal group at its PEG end and a methacryloyl group at its PLA end (acetal-PEG-b-PLA-MA) was performed in an aqueous medium. As the acetal-PEG-b-PLA-MA forms a polymeric micelle in an aqueous medium, the carborane monomer in the hydrophobic core is solubilized, and the carborane in the core of the micelle is given covalent conjunction. Two carborane compounds, carborane with a mono-vinylbenzyl group [1-(4-vinylbenzyl)-closo-carborane (VB-carborane)] and carborane with di-vinylbenzyl groups [1,2-bis(4-vinylbenzyl)-closo-carborane ((VB)2-carborane)], were newly prepared and employed for the core polymerizations. The encapsulation efficiency of the VB-carborane in the micelles is much higher than that of the (VB)2-carborane. This improved efficiency is most likely caused by the interaction of the hydrogen bonding of the VB-carborane with the polymer micelle matrix, while no hydrogen bonding sites remain in the case of the (VB)2-carborane. The obtained core-polymerized and boron-conjugated micelles (PM, which were prepared from VB-carborane) showed extremely high stability under physiological conditions, which suppressed the leakage of boron compounds owing to the existence of the covalent bonds. The accumulation of the PM (7.2 ID% per g) in tumors is much higher than that of the non-polymerized micelles (NPM) (0.7 ID% per g) under the same conditions (at 24 h after injection) because of the enhanced stability of the micelles under physiological conditions. In addition, thermal neutron irradiation experiments indicated significant suppression of the growth of tumor volume in tumor-bearing mice treated with the PM. It is important to note that the PM administered via intravenous injection were excreted almost completely from the major organs, except for the tumor, after a week. Therefore, these boron-conjugated micelles represent a promising approach to the creation of a novel boron carrier for BNCT. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Polymer Journal Springer Journals

Boron neutron capture therapy assisted by boron-conjugated nanoparticles

Sumitani, Shogo; Nagasaki, Yukio
Polymer Journal , Volume 44 (6) – Apr 4, 2012
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References (68)

Publisher
Springer Journals
Copyright
Copyright © 2012 by The Society of Polymer Science, Japan
Subject
Chemistry; Chemistry/Food Science, general; Polymer Sciences; Biomaterials; Surfaces and Interfaces, Thin Films; Bioorganic Chemistry
ISSN
0032-3896
eISSN
1349-0540
DOI
10.1038/pj.2012.30
Publisher site
See Article on Publisher Site

Abstract

For high-performance boron neutron capture therapy (BNCT), core-shell-type biodegradable nanoparticles possessing boron clusters in their cores are designed to improve their accumulation tendency in the tumor region. The copolymerization of styrene carrying carborane with a poly(ethylene glycol)-block-poly(lactide) copolymer (PEG-b-PLA) that possesses an acetal group at its PEG end and a methacryloyl group at its PLA end (acetal-PEG-b-PLA-MA) was performed in an aqueous medium. As the acetal-PEG-b-PLA-MA forms a polymeric micelle in an aqueous medium, the carborane monomer in the hydrophobic core is solubilized, and the carborane in the core of the micelle is given covalent conjunction. Two carborane compounds, carborane with a mono-vinylbenzyl group [1-(4-vinylbenzyl)-closo-carborane (VB-carborane)] and carborane with di-vinylbenzyl groups [1,2-bis(4-vinylbenzyl)-closo-carborane ((VB)2-carborane)], were newly prepared and employed for the core polymerizations. The encapsulation efficiency of the VB-carborane in the micelles is much higher than that of the (VB)2-carborane. This improved efficiency is most likely caused by the interaction of the hydrogen bonding of the VB-carborane with the polymer micelle matrix, while no hydrogen bonding sites remain in the case of the (VB)2-carborane. The obtained core-polymerized and boron-conjugated micelles (PM, which were prepared from VB-carborane) showed extremely high stability under physiological conditions, which suppressed the leakage of boron compounds owing to the existence of the covalent bonds. The accumulation of the PM (7.2 ID% per g) in tumors is much higher than that of the non-polymerized micelles (NPM) (0.7 ID% per g) under the same conditions (at 24 h after injection) because of the enhanced stability of the micelles under physiological conditions. In addition, thermal neutron irradiation experiments indicated significant suppression of the growth of tumor volume in tumor-bearing mice treated with the PM. It is important to note that the PM administered via intravenous injection were excreted almost completely from the major organs, except for the tumor, after a week. Therefore, these boron-conjugated micelles represent a promising approach to the creation of a novel boron carrier for BNCT.

Journal

Polymer Journal – Springer Journals

Published: Apr 4, 2012

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