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

• Main Authors: Jackson, Alexander W., Chandrasekharan, Prashant, Shi, Jian, Rannard, Steven P., Liu, Quan, Yang, Chang-Tong, He, Tao
• Other Authors: School of Chemical and Biomedical Engineering
• Format: Article
• Language: English
• Published: 2015
• Subjects: MRI; RAFT polymerization; branched copolymer nanoparticles; gadolinium chelate
• Online Access: https://hdl.handle.net/10356/81040; http://hdl.handle.net/10220/39076
• Institution: Nanyang Technological University

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.