Synthesis and in vivo magnetic resonance imaging evaluation of biocompatible branched copolymer nanocontrast agents

Alexander W Jackson,1,* Prashant Chandrasekharan,2,* Jian Shi,3 Steven P Rannard,4 Quan Liu,5 Chang-Tong Yang,6 Tao He1,7 1Institute of Chemical and Engineering Sciences (ICES), 2Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Agency for Science Technology and Research (A*&nbs...

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Autores principales: Jackson AW, Chandrasekharan P, Shi J, Rannard SP, Liu Q, Yang CT, He T
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Publicado: Dove Medical Press 2015
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spelling oai:doaj.org-article:5239389086fe41d7b7ee03f1435237db2021-12-02T03:11:42ZSynthesis and in vivo magnetic resonance imaging evaluation of biocompatible branched copolymer nanocontrast agents1178-2013https://doaj.org/article/5239389086fe41d7b7ee03f1435237db2015-09-01T00:00:00Zhttps://www.dovepress.com/synthesis-and-in-vivo-magnetic-resonance-imaging-evaluation-of-biocomp-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Alexander W Jackson,1,* Prashant Chandrasekharan,2,* Jian Shi,3 Steven P Rannard,4 Quan Liu,5 Chang-Tong Yang,6 Tao He1,7 1Institute of Chemical and Engineering Sciences (ICES), 2Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Agency for Science Technology and Research (A* STAR), 3Department of Biological Science, National University of Singapore, Singapore; 4Department of Chemistry, University of Liverpool, Liverpool, United Kingdom; 5School of Chemical and Biomedical Engineering, 6Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; 7School of Chemistry and Chemical Engineering, HeFei University of Technology, Anhui, People’s Republic of China *These authors contributed equally to this work Abstract: Branched copolymer nanoparticles (Dh =20–35 nm) possessing 1,4,7, 10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid macrocycles within their cores have been synthesized and applied as magnetic resonance imaging (MRI) nanosized contrast agents in vivo. These nanoparticles have been generated from novel functional monomers via reversible addition–fragmentation chain transfer polymerization. The process is very robust and synthetically straightforward. Chelation with gadolinium and preliminary in vivo experiments have demonstrated promising characteristics as MRI contrast agents with prolonged blood retention time, good biocompatibility, and an intravascular distribution. The ability of these nanoparticles to perfuse and passively target tumor cells through the enhanced permeability and retention effect is also demonstrated. These novel highly functional nanoparticle platforms have succinimidyl ester-activated benzoate functionalities within their corona, which make them suitable for future peptide conjugation and subsequent active cell-targeted MRI or the conjugation of fluorophores for bimodal imaging. We have also demonstrated that these branched copolymer nanoparticles are able to noncovalently encapsulate hydrophobic guest molecules, which could allow simultaneous bioimaging and drug delivery. Keywords: branched copolymer nanoparticles, gadolinium chelate, MRI, RAFT polymerizationJackson AWChandrasekharan PShi JRannard SPLiu QYang CTHe TDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 5895-5907 (2015)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Jackson AW
Chandrasekharan P
Shi J
Rannard SP
Liu Q
Yang CT
He T
Synthesis and in vivo magnetic resonance imaging evaluation of biocompatible branched copolymer nanocontrast agents
description Alexander W Jackson,1,* Prashant Chandrasekharan,2,* Jian Shi,3 Steven P Rannard,4 Quan Liu,5 Chang-Tong Yang,6 Tao He1,7 1Institute of Chemical and Engineering Sciences (ICES), 2Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Agency for Science Technology and Research (A* STAR), 3Department of Biological Science, National University of Singapore, Singapore; 4Department of Chemistry, University of Liverpool, Liverpool, United Kingdom; 5School of Chemical and Biomedical Engineering, 6Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; 7School of Chemistry and Chemical Engineering, HeFei University of Technology, Anhui, People’s Republic of China *These authors contributed equally to this work Abstract: Branched copolymer nanoparticles (Dh =20–35 nm) possessing 1,4,7, 10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid macrocycles within their cores have been synthesized and applied as magnetic resonance imaging (MRI) nanosized contrast agents in vivo. These nanoparticles have been generated from novel functional monomers via reversible addition–fragmentation chain transfer polymerization. The process is very robust and synthetically straightforward. Chelation with gadolinium and preliminary in vivo experiments have demonstrated promising characteristics as MRI contrast agents with prolonged blood retention time, good biocompatibility, and an intravascular distribution. The ability of these nanoparticles to perfuse and passively target tumor cells through the enhanced permeability and retention effect is also demonstrated. These novel highly functional nanoparticle platforms have succinimidyl ester-activated benzoate functionalities within their corona, which make them suitable for future peptide conjugation and subsequent active cell-targeted MRI or the conjugation of fluorophores for bimodal imaging. We have also demonstrated that these branched copolymer nanoparticles are able to noncovalently encapsulate hydrophobic guest molecules, which could allow simultaneous bioimaging and drug delivery. Keywords: branched copolymer nanoparticles, gadolinium chelate, MRI, RAFT polymerization
format article
author Jackson AW
Chandrasekharan P
Shi J
Rannard SP
Liu Q
Yang CT
He T
author_facet Jackson AW
Chandrasekharan P
Shi J
Rannard SP
Liu Q
Yang CT
He T
author_sort Jackson AW
title Synthesis and in vivo magnetic resonance imaging evaluation of biocompatible branched copolymer nanocontrast agents
title_short Synthesis and in vivo magnetic resonance imaging evaluation of biocompatible branched copolymer nanocontrast agents
title_full Synthesis and in vivo magnetic resonance imaging evaluation of biocompatible branched copolymer nanocontrast agents
title_fullStr Synthesis and in vivo magnetic resonance imaging evaluation of biocompatible branched copolymer nanocontrast agents
title_full_unstemmed Synthesis and in vivo magnetic resonance imaging evaluation of biocompatible branched copolymer nanocontrast agents
title_sort synthesis and in vivo magnetic resonance imaging evaluation of biocompatible branched copolymer nanocontrast agents
publisher Dove Medical Press
publishDate 2015
url https://doaj.org/article/5239389086fe41d7b7ee03f1435237db
work_keys_str_mv AT jacksonaw synthesisandinvivomagneticresonanceimagingevaluationofbiocompatiblebranchedcopolymernanocontrastagents
AT chandrasekharanp synthesisandinvivomagneticresonanceimagingevaluationofbiocompatiblebranchedcopolymernanocontrastagents
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