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

Authors Jackson AW, Chandrasekharan P, Shi J, Rannard SP, Liu Q, Yang CT, He T

Received 18 May 2015

Accepted for publication 30 June 2015

Published 18 September 2015 Volume 2015:10(1) Pages 5895—5907

DOI https://doi.org/10.2147/IJN.S88764

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Jia Fan

Peer reviewer comments 6

Editor who approved publication: Dr Thomas J Webster

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

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