title: Synthesis and in vivo magnetic resonance imaging evaluation of biocompatible branched copolymer nanocontrast agents.
abstract: Branched copolymer nanoparticles (D(h) =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.
authors.affiliation: Institute of Chemical and Engineering Sciences (ICES), National University of Singapore, Singapore.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Jackson
authors.affiliation: Laboratory of Molecular Imaging, Singapore Bioimaging Consortium, Agency for Science Technology and Research(A STAR), National University of Singapore, Singapore.
authors.forename: Prashant
authors.initials: P
authors.lastname: Chandrasekharan
authors.affiliation: Department of Biological Science, National University of Singapore, Singapore.
authors.forename: Jian
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Chemistry, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Rannard
authors.affiliation: School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.
authors.forename: Quan
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
authors.forename: Chang-Tong
authors.initials: CT
authors.lastname: Yang
authors.affiliation: Institute of Chemical and Engineering Sciences (ICES), National University of Singapore, Singapore ; School of Chemistryand Chemical Engineering, HeFei University of Technology, Anhui, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: He
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D002614:Chelating Agents / Q000737:chemistry; D003287:Contrast Media / Q000737:chemistry*; D016503:Drug Delivery Systems; D005260:Female; D005682:Gadolinium / Q000737:chemistry; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D016513:Mice, SCID; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry; D058105:Polymerization; D011108:Polymers / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D002614:Chelating Agents; D003287:Contrast Media; D008823:Micelles; D011108:Polymers; D005682:Gadolinium
keywords: MRI; RAFT polymerization; branched copolymer nanoparticles; gadolinium chelate