Cell uptake and in vitro toxicity of magnetic nanoparticles suitable for drug delivery.

Magnetic targeting is useful for intravascular or intracavitary drug delivery, including tumor chemotherapy or intraocular antiangiogenic therapy. For all such in vivo applications, the magnetic drug carrier must be biocompatible and nontoxic. In this work, we investigated the toxic properties of magnetic nanoparticles coated with polyethylenoxide (PEO) triblock copolymers. Such coatings prevent the aggregation of magnetic nanoparticles and guarantee consistent magnetic and nonmagnetic flow properties. It was found that the PEO tail block length inversely correlates with toxicity. The nanoparticles with the shortest 0.75 kDa PEO tails were the most toxic, while particles coated with the 15 kDa PEO tail block copolymers were the least toxic. Toxicity responses of the tested prostate cancer cell lines (PC3 and C4-2), human umbilical vein endothelial cells (HUVECs), and human retinal pigment epithelial cells (HRPEs) were similar. Furthermore, all cell types took up the coated magnetic nanoparticles. It is concluded that magnetite nanoparticles coated with triblock copolymers containing PEO tail lengths of above 2 kDa are biocompatible and appropriate for in vivo application.

Aqueous dispersions of magnetite nanoparticles complexed with copolyether dispersants: experiments and theory.

Magnetite (Fe3O4) nanoparticles have been synthesized and complexed with carboxylate-functional block copolymers, and then aqueous dispersions of the complexes were investigated as functions of their chemical and morphological structures. The block copolymer dispersants had either poly(ethylene oxide), poly(ethylene oxide-co-propylene oxide), or poly(ethylene oxide-b-propylene oxide) outer blocks, and all of them had a polyurethane center block that contained pendent carboxylate groups. The complexes were formed through interactions of the carboxylates with the surfaces of the magnetite nanoparticles. The magnetite cores of the magnetite-copolymer complexes were near 10 nm in diameter, and the particles were superparamagnetic. Complexes with mass ratios of polymer to magnetite varying from 50:50 to 85:15 were studied. One of our objectives is to design complexes that form stable dispersions of discrete particles in water, yet that can be actuated (moved together) upon exposure to a uniform magnetic field. DLVO calculations that accounted for magnetic attractive interparticle forces, as well as van der Waals, steric, and electrostatic forces are presented. Compositions were identified wherein a shallow, attractive interparticle potential minimum appears once the magnetic term is applied. This suggests that it may be possible to tune the structures of superparamagnetic nanoparticle shells to allow discrete dispersions without a field, yet weak flocculation could be induced upon exposure to a field.