Development of europium doped core-shell silica cobalt ferrite functionalized nanoparticles for magnetic resonance imaging

• Published in: Acta biomaterialia Vol. 49; pp. 507 - 520
• Main Authors: Kevadiya, Bhavesh D., Bade, Aditya N., Woldstad, Christopher, Edagwa, Benson J., McMillan, JoEllyn M., Sajja, Balasrinivasa R., Boska, Michael D., Gendelman, Howard E.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2017; Elsevier BV
• Subjects: Animals; Biodistribution; Chemical elements; Cobalt; Cobalt - chemistry; Cobalt ferrite; Cobalt ferrites; Endocytosis; Europium; Europium - chemistry; Ferric Compounds - chemistry; Fluorescence; Folic acid; Folic Acid - chemistry; Humans; Immunohistochemistry; Iron; Iron oxides; Macrophages; Macrophages - metabolism; Macrophages - ultrastructure; Magnetic properties; Magnetic Resonance Imaging; Male; Medical imaging; Microscopy, Atomic Force; Microscopy, Confocal; Monocyte-macrophages; Monocytes; Monocytes - cytology; Multimodal imaging; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - toxicity; Nanoprobes; NMR; Nuclear magnetic resonance; Particulates; Rats, Sprague-Dawley; Resonance; Silica; Silicon dioxide; Silicon Dioxide - chemistry; Spectroscopy, Fourier Transform Infrared; Studies; Thermogravimetry; Tissue Distribution; Multimodal imaging; Monocyte-macrophages; Nanoprobes; Magnetic resonance imaging; Biodistribution; Cobalt ferrite
• ISSN: 1742-7061; 1878-7568; 1878-7568
• DOI: 10.1016/j.actbio.2016.11.071

[Display omitted] The size, shape and chemical composition of europium (Eu3+) cobalt ferrite (CFEu) nanoparticles were optimized for use as a “multimodal imaging nanoprobe” for combined fluorescence and magnetic resonance bioimaging. Doping Eu3+ ions into a CF structure imparts unique bioimaging and magnetic properties to the nanostructure that can be used for real-time screening of targeted nanoformulations for tissue biodistribution assessment. The CFEu nanoparticles (size ∼7.2nm) were prepared by solvothermal techniques and encapsulated into poloxamer 407-coated mesoporous silica (Si-P407) to form superparamagnetic monodisperse Si-CFEu nanoparticles with a size of ∼140nm. Folic acid (FA) nanoparticle decoration (FA-Si-CFEu, size ∼140nm) facilitated monocyte-derived macrophage (MDM) targeting. FA-Si-CFEu MDM uptake and retention was higher than seen with Si-CFEu nanoparticles. The transverse relaxivity of both Si-CFEu and FA-Si-CFEu particles were r2=433.42mM−1s−1 and r2=419.52mM−1s−1 (in saline) and r2=736.57mM−1s−1 and r2=814.41mM−1s−1 (in MDM), respectively. The results were greater than a log order-of-magnitude than what was observed at replicate iron concentrations for ultrasmall superparamagnetic iron oxide (USPIO) particles (r2=31.15mM−1s−1 in saline) and paralleled data sets obtained for T2 magnetic resonance imaging. We now provide a developmental opportunity to employ these novel particles for theranostic drug distribution and efficacy evaluations. A novel europium (Eu3+) doped cobalt ferrite (Si-CFEu) nanoparticle was produced for use as a bioimaging probe. Its notable multifunctional, fluorescence and imaging properties, allows rapid screening of future drug biodistribution. Decoration of the Si-CFEu particles with folic acid increased its sensitivity and specificity for magnetic resonance imaging over a more conventional ultrasmall superparamagnetic iron oxide particles. The future use of these particles in theranostic tests will serve as a platform for designing improved drug delivery strategies to combat inflammatory and infectious diseases.