Delayed hepatic uptake of multi-phosphonic acid poly(ethylene glycol) coated iron oxide measured by real-time Magnetic Resonance Imaging
نویسندگان
چکیده
We report on the synthesis, characterization, stability and pharmacokinetics of novel iron based contrast agents for magnetic resonance imaging (MRI). Statistical copolymers combining multiple phosphonic acid groups and poly(ethylene glycol) (PEG) were synthesized and used as coating agents for 10 nm iron oxide nanocrystals. In vitro, protein corona and stability assays show that phosphonic acid PEG copolymers outperform all other coating types examined, including low molecular weight anionic ligands and polymers. In vivo, the particle pharmacokinetics is investigated by monitoring the MRI signal intensity from mouse liver, spleen and arteries as a function of the time, between one minute and seven days after injection. Iron oxide particles coated with multi-phosphonic acid PEG polymers are shown to have a blood circulation lifetime of 250 minutes, i.e. 10 to 50 times greater than that of recently published PEGylated probes and benchmarks. The clearance from the liver takes in average 2 to 3 days and is independent of the core size, coating and particle stability. By comparing identical core particles with different coatings, we are able to determine the optimum conditions for stealth MRI probes. keywords: Magnetic resonance imaging Contrast agents Iron oxide nanoparticles PEGylated coating – Pharmacokinetics Journal RSC Advances, 2016, DOI: 10.1039/C6RA09896G Corresponding author [email protected] Submitted to Cond-Mat Saturday, July 2, 2016
منابع مشابه
ANALYTICAL STUDY OF EFFECT OF BILAYER INORGANIC AND ORGANIC COATING AROUND THE IRON OXIDE NANOPARTICLES ON MAGNETIC RESONANCE IMAGING CONTRAST
Background & Aims: In recent years, iron oxide nanoparticles have been used in contrast-enhanced magnetic resonance imaging for diagnosing a wide range of diseases. In order to provide biocompatibility and prevent the toxicity of the nanoparticles, using organic or inorganic coating around these nanoparticles is important for their application. The aim of this study is to investigate the effect...
متن کاملPEG-b-AGE Polymer Coated Magnetic Nanoparticle Probes with Facile Functionalization and Anti-fouling Properties for Reducing Non-specific Uptake and Improving Biomarker Targeting.
Non-specific surface adsorption of bio-macromolecules (e.g. proteins) on nanoparticles, known as biofouling, and the uptake of nanoparticles by the mononuclear phagocyte system (MPS) and reticuloendothelial system (RES) lead to substantial reduction in the efficiency of target-directed imaging and delivery in biomedical applications of engineered nanomaterials in vitro and in vivo. In this work...
متن کاملPreventing corona effects: multiphosphonic acid poly(ethylene glycol) copolymers for stable stealth iron oxide nanoparticles.
When dispersed in biological fluids, engineered nanoparticles are selectively coated with proteins, resulting in the formation of a protein corona. It is suggested that the protein corona is critical in regulating the conditions of entry into the cytoplasm of living cells. Recent reports describe this phenomenon as ubiquitous and independent of the nature of the particle. For nanomedicine appli...
متن کاملIntracellular uptake of folate receptor targeted superparamagnetic nanoparticles for enhanced tumor detection by MRI
Folic acid (FA) was conjugated to superparamagnetic iron oxide nanoparticles to develop a tumor specific contrast agent for magnetic resonance imaging (MRI). In this scheme a bifunctional poly(ethylene glycol) (PEG) linker was utilized to both increase biocompatibility and reduce nanoparticle agglomeration. The uptake of nanoparticle-PEG-FA conjugates by folate-receptor (FR) positive MCF-7 cell...
متن کاملEffect of coating thickness of iron oxide nanoparticles on their relaxivity in the MRI
Objective(s):Iron oxide nanoparticles have found prevalent applications in various fields including drug delivery, cell separation and as contrast agents. Super paramagnetic iron oxide (SPIO) nanoparticles allow researchers and clinicians to enhance the tissue contrast of an area of interest by increasing the relaxation rate of water. In this study, we evaluate the dependency of hydrodynamic si...
متن کامل