ABSTRACT
Human serum albumin (HSA) is a protein found in human blood. Over the last decade, HSA has been evaluated as a promising drug carrier. However, not being magnetic, HSA cannot be used for biomedical applications such as magnetic resonance imaging (MRI) and magnetic drug targeting. Therefore, subsequent composites building on iron oxide nanoparticles that are already used clinically as MRI contrast agents are extensively studied. Recently and in this context, innovative fully hydrophilic ultra-small CAN-stabilized maghemite ((CeLn)(3/4+)-γ-Fe2O3) nanoparticles have been readily fabricated. The present study discusses the design, fabrication, and characterization of a dual phase hybrid core (rHSA)-shell ((CeLn)(3/4+)-γ-Fe2O3 NPs) nanosystem. Quite importantly and in contrast to widely used encapsulation strategies, rHSA NP surface-attached (CeLn)(3/4+)-γ-Fe2O3 NPs enabled to exploit both rHSA (protein functionalities) and (CeLn)(3/4+)-γ-Fe2O3 NP surface functionalities (COOH and ligand L coordinative exchange) in addition to very effective MRI contrast capability due to optimal accessibility of H2O molecules with the outer magnetic phase. Resulting hybrid nanoparticles might be used as a platform modular system for therapeutic (drug delivery system) and MR diagnostic purposes.
Subject(s)
Biocompatible Materials/chemical synthesis , Magnetite Nanoparticles/chemistry , Serum Albumin/chemistry , Cations , Contrast Media/chemical synthesis , Humans , Magnetite Nanoparticles/toxicity , Materials TestingABSTRACT
Iron oxide-containing magnetic nanoparticles (MNPs) have certain advantages over currently used contrast agents for tumor imaging by magnetic resonance imaging (MRI) as they offer the possibility of functionalization with ligands and tracers. Functionalized MNPs also may be used for targeted tumor therapy. In the current study nanoparticles (NPs) consisting of recombinant human serum albumin (rHSA) with incorporated hydrophilic (NH4)2Ce(IV)(NO3)6-γ-Fe2O3 particles (CAN maghemite particles) for medical imaging were produced and characterized. For this purpose CAN maghemite particles were incorporated into an rHSA matrix to yield rHSA-NPs. The resulting NPs were analyzed by transmission electron microscopy, photon correlation spectroscopy, and atomic absorption. The sizes of the manufactured NP were 170 ± 10 nm, and the zeta-potential was -50 ± 3 mV. The NPs remained stable when stored after lyophilization with sucrose 3% [w/v] as a cryoprotector. They showed pro-inflammatory properties without cell and animal toxicity in vivo and were highly contrasting in MRI. In conclusion, this report introduces novel rHSA NP with favorable properties containing iron oxide for detection by MRI.
Subject(s)
Contrast Media , Diagnostic Imaging/methods , Ferric Compounds , Magnetite Nanoparticles , Serum Albumin , Animals , Cell Line, Tumor , Cell Survival/drug effects , Contrast Media/administration & dosage , Contrast Media/toxicity , Drug Stability , Electrochemistry , Ferric Compounds/administration & dosage , Ferric Compounds/chemistry , Ferric Compounds/toxicity , Humans , Magnetic Resonance Imaging , Magnetics , Magnetite Nanoparticles/administration & dosage , Magnetite Nanoparticles/toxicity , Male , Mice , Mice, Inbred C57BL , Mice, Inbred ICR , Neoplasms/diagnosis , Particle Size , Recombinant Proteins/administration & dosage , Recombinant Proteins/toxicity , Serum Albumin/administration & dosage , Serum Albumin/toxicityABSTRACT
The need for test systems for nanoparticle biocompatibility, toxicity, and inflammatory or adaptive immunological responses is paramount. Nanoparticles should be free of microbiological and chemical contaminants, and devoid of toxicity. Nevertheless, in the absence of contamination, these particles may still induce undesired immunological effects in vivo, such as enhanced autoimmunity, hypersensitivity reactions, and fibrosis. Here we show that artificial particles of specific sizes affect immune cell recruitment as tested in a dermal air pouch model in mice. In addition, we demonstrate that the composition of nanoparticles may influence immune cell recruitment in vivo. Aside from biophysical characterizations in terms of hydrodynamic diameter, zeta potential, concentration, and atomic concentration of metals, we show that - after first-line in vitro assays - characterization of cellular and molecular effects by dermal air pouch analysis is straightforward and should be included in the quality control of nanoparticles. We demonstrate this for innate immunological effects such as neutrophil recruitment and the production of immune-modulating matrix metalloproteases such as MMP-9; we propose the use of air pouch leukocytosis analysis as a future standard assay.