Dendrimer-Coated Iron Oxide Nanoparticlees as Targeted MRI Contrast Agents.

[摘要] Targeted MRI contrast agents are anticipated to be critical tools in realizing the dream of predictive and preventative medicine.Many approaches have been documented regarding superparamagnetic iron oxide nanoparticles (SPIONs) as contrast agents and the use of various ligands to actively target them to specific tissues.This dissertation explores SPIONs coated and targeted by functionalized dendrimers for specific uptake by cancer cells via the folic acid receptor (FAR).Monodisperse SPIONs were first prepared in organic solvents (OC-SPIONs).Amine-terminated generation 5 poly(amidoamine) (G5-PAMAM) dendrimers were conjugated with an average of five folic acid (FA) moieties for targeting and three 6-TAMRA (6T) dye molecules for tracking by optical fluorescence.To minimize nonspecific interactions, the remaining amino groups were neutralized by capping with acetyl (Ac) groups.The resulting polymer units, G5-Ac(102)-FA(5)-6T(3), were used to transfer OC-SPIONs from organic to aqueous media, imparting protection, biocompatibility, optical tracking and targeting in a single step.Following phase transfer, the dendrimer-coated SPIONs (DC-SPIONs) exhibited key properties for effective contrast agents: they retained their size and shape uniformity and exhibited a high saturation magnetization.The ability of the dendrimer-coated SPIONs (DC-SPIONs) to be specifically internalized by cancer cells overexpressing the FAR was confirmed and quantified in vitro.Targeted uptake of the dendrimer coatings and SPION cores was independently verified by two distinct but complementary techniques: flow cytometry for the dendrimers (6-TAMRA signal) and X-ray fluorescence (XRF) microscopy for the SPIONs (elemental iron signal).Using XRF microscopy is unique because it enables quantification of iron uptake at the single-cell level versus analysis on bulk cell samples.The XRF microscopy data reveal a wide variation in iron uptake that correlates well with the uptake distribution from flow cytometry and is consistent with the variability in uptake observed for neat G5-Ac(102)-FA(5)-6T(3).

[发布机构] University of Michigan

[效力级别] Cancer

[关键词] Magnetic Nanoparticles;Cancer;Targeted MRI Contrast Agents;X-ray Fluorescence Microscopy;Superparamagnetism;Phase Transfer;Physics;Science;Applied Physics