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Effective treatment of brain disorders requires a focus on improving drug permeability across the blood-brain barrier (BBB). Herein, we examined the pharmacokinetic properties of negatively charged iron oxide nanoparticles (IONPs) and the capability of using lysophosphatidic acid (LPA) to transiently disrupt the tight junctions and allow IONPs to enter the brain. Under normal conditions, IONPs had a plasma half-life of six minutes, with the liver and spleen being the major organs of deposition. Treatment with LPA enhanced accumulation of IONPs in the brain and spleen (approximately 4-fold vs. control). LPA and IONP treated mice revealed no sign of peripheral immune cell infiltration in the brain and no significant activation of microglia or astrocytes. These studies show improved delivery efficiency of IONPs following LPA administration. Our findings suggest transient disruption of the BBB may be a safe and effective method for increasing IONP delivery to the brain., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Iron oxide nanoparticles (IONPs) and their surface modifications with therapeutic or diagnostic (theranostic, TN) agents are of great interest. Here we present a novel one-pot synthesis of a versatile general TN precursor (aminosilane-coated IONPs [IONP-Sil(NH2)]) with surface amine groups. Surface functional group conversion to carboxylic acid was accomplished by conjugating poly(ethylene glycol) diacid to IONP-Sil(NH2). The NPs were characterized using powder X-ray diffraction (XRD), transmission electron microscopy (TEM), high-resolution TEM, selected area electron diffraction (SAED), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FT-IR) spectroscopy. Biocompatibility and cell uptake profile of the nanoparticles were evaluated in-vitro using cultured liver cells (HepG2). Oleylamine (hydrophobic) and bovine serum albumin (BSA) as model drugs were attached to IONP-Sil-PEG(COOH). The ability of IONP-Sil(NH2) to bind small interfering RNA (siRNA) is also shown.