Interaction of Functionalized Superparamagnetic Iron Oxide Nanoparticles with Brain Structures

Abstract

Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) combined with magnetic resonance imaging (MRI) are under clinical evaluation to enhance detection of neurodegenerative diseases. A major improvement would be to link therapeutic drugs to the SPIONs to achieve targeted drug delivery, either at the cell surface or intracellularly, together with active disease detection, without inducing cell reaction. Our objectives were to define the characteristics of SPIONS able to achieve cell-specific interaction with brain-derived structures. Our system consisted in an iron oxide core (9 -10 nm diameter) coated either with dextran (Sinerem and Endorem) or various functionalized polyvinyl alcohols (PVAs) (PVA-SPIONs). We investigated the cellular uptake, cytotoxicity, and interaction of these various nanoparticles with brain-derived endothelial cells, microglial cells, and differentiating three-dimensional aggregates. None of the nanoparticles coated with dextran or the various PVAs was cytotoxic or induced the production of the inflammatory mediator NO used as a reporter for cell activation. AminoPVASPIONs were taken up by isolated brain-derived endothelial and microglial cells at a much higher level than the other SPIONs, and no inflammatory activation of these cells was observed. AminoPVA-SPIONs did not invade brain cells aggregates lower than the first cell layer and did not induce inflammatory reaction in the aggregates. Fluorescent aminoPVASPIONs derivatized with a fluorescent reporter molecule and confocal microscopy demonstrated intracellular uptake by microglial cells. Fluorescent aminoPVA-SPIONs were well tolerated by mice. Therefore, functionalized aminoPVA-SPIONs represent biocompatible potential vector systems for drug delivery to the brain that may be combined with MRI detection of active lesions in neurodegenerative diseases.Nanotechnologies and nanostructures are becoming an option in human medical application, including imaging or the delivery of therapeutic drugs to cells, tissues, and organs. Most of these latter applications would require that drugloaded nanoparticles enter organ and tissues and are taken up by cells. Several studies have shown that the tissue, cell, and even cell organelle distribution (Alexiou et al., 2000;Savic et al., 2003) of drugs may be controlled and improved by their entrapment in colloidal nanomaterials, mainly of the micellar structure, such as nanocontainers. The development of a large variety of colloidal dispersions of Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) has added a supplementary function to nanomaterials, their magnetic properties, which can lead to a range of new biological, biomedical, and diagnostic applications. In particular, the application of the different forms of iron oxides for radiological diagnostic procedures to document vascular leakage, macrophage imaging, or cell tracking (Weissleder et al

The endocytic penetration mechanism of iron oxide magnetic nanoparticles with positively charged cover: A morphological approach

“…However, positive NPs coated with AD were rapidly internalized in cells, and lack of toxicity was observed (11). Similar results were obtained for amino polyvinyl alcohol coated nanoparticles that showed a much higher uptake by cerebral cells, absence of cytotoxicity and in vivo biocompatibility (18).…”

Superparamagnetic iron oxide nanoparticles: magnetic nanoplatforms as drug carriers

“…These SPIONs were also found to be biocompatible, producing no inflammatory response in brain-derived cell cultures. 131 Coating of SPIONs with appropriate polymers combined with application of a strong external magnetic field could lead to development of a potential vector for imaging and treatment of neurodegenerative diseases.…”

Chitosan-based nanogels for selective delivery of photosensitizers to macrophages and improved retention in and therapy of articular joints

“…The demonstrated absence of secretion of NO by murine macrophages incubated with the PS-nanogels confirmed this important property of the nanogels. Comparable information had been previously obtained using other types of nanoparticles, including dextran-coated ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles used in clinics as MRI contrast agents [39].…”