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.

Polymerizable Gd(iii) building blocks for the synthesis of high relaxivity macromolecular MRI contrast agents

“…Of the very few reported macromolecular CAs wherein the Gd(III) complex behaves as a crosslinker, [68][69][70] our system is the only example which takes advantages of the crosslinking to efficiently reduce the local rotational tumbling. This leads to higher relaxivity than those previously reported (e.g.…”

Activatable Cell-Penetrating Peptide Conjugated Polymeric Nanoparticles with Gd-Chelation and Aggregation-Induced Emission for Bimodal MR and Fluorescence Imaging of Tumors

“…Initial in vivo imaging studies of N-BP5-Gd-ACPPs using xenografts of the mice model bearing a HepG2 tumor demonstrated considerable accumulation in the HepG2 tumor at 15 min postinjection as shown in Figure a, which was much faster than the similar-sized nanoparticles without ACPPs (Figure b). The size of nanoparticle (40 nm) and oligo (ethylene glycol) methyl ether methacrylate-based coronas, which are known to prevent opsonization and uptake by the reticuloendothelial system, could lead to a long blood circulation time of these nanoparticles. Accumulation remained high in the tumor at 30 min postinjection, which indicated that cleaved cation nanoparticles would be involved in potential membrane binding such as blood vessels and connective tissues.…”

Complex polymer architectures through free-radical polymerization of multivinyl monomers

“…148 The introduction of degradable branching points into a high molecular weight PDMAEMA, has been shown to overcome the long-standing, and problematic, correlation between transfection efficacy and toxicity 149 Similar topological effects have also been observed in other biomedical applications of polymers. 150,151 Bacterial contamination on medical device surfaces is a major safety issue in hospitals. Single-chain cyclized polymers were used to fabricate coatings which suppressed the formation of a biofilm.…”