Molecularly imprinted polymer nanoparticles (nanoMIPs) are high affinity synthetic receptors which show promise as imaging and therapeutic agents. Comprehensive analysis of the in vivo behaviour of nanoMIPs must be performed before they can be considered for clinical applications. This work reports the solid-phase synthesis of nanoMIPs and an investigation of their biodistribution, clearance and cytotoxicity in a rat model following both intravenous and oral administration. These nanoMIPs were found in each harvested tissue type, including brain tissue, implying their ability to cross the blood–brain barrier. The nanoMIPs were cleared from the body via both faeces and urine. Furthermore, we describe an immunogenicity study in mice, demonstrating that nanoMIPs specific for a cell surface protein showed moderate adjuvant properties, whilst those imprinted for a scrambled peptide showed no such behaviour. Given their ability to access all tissue types and their relatively low cytotoxicity, these results pave the way for in vivo applications of nanoMIPs.
Herein, we assess the dose-dependent antioxidant efficacy of ultrafine spherical functionalized core–shell yttrium oxide nanoparticles (YNPs) with a mean size of 7–8 nm and modified with poly EGMP (ethylene glycol methacrylate phosphate) and N-Fluorescein Acrylamide. The antioxidant properties of these nanoparticles were investigated in three groups of Sprague–Dawley rats (10 per group) exposed to environmental stress daily for 1 week and one control group. Groups 2 and 3 were intravenously injected twice a week with YNPs at 0.3 and 0.5 mg at 2nd and 5th day of environmental stress exposure respectively. Different samples of blood and serum were collected from all experimental groups at end of the experiment to measure oxidative biomarkers such as total antioxidant capacity (TAC), hydroxyl radical antioxidant capacity (HORAC), oxygen radical antioxidant capacity (ORAC), malondialdehyde (MDA), and oxidants concentration as hydrogen peroxide (H2O2). The liver, brain, and spleen tissues were collected for fluorescence imaging and histopathological examination in addition to brain tissue examination by transmission electron microscope (TEM). Inductively coupled plasma-mass spectrometry (ICP-MS) was used to estimate YNPs translocation and concentration in tissues which is consecutively dependent on the dose of administration. Depending on all results, poly EGMP YNPs (poly EGMP yttrium oxide nanoparticles) can act as a potent direct antioxidant in a dose-dependent manner with good permeability through blood–brain barrier (BBB). Also, the neuroprotective effect of YNPs opening the door to a new therapeutic approach for modulating oxidative stress–related neural disorders.
Highlights
• The dose-dependent antioxidant efficacy of ultrafine spherical functionalized core–shell yttrium oxide nanoparticles (YNPs) with a mean size of 7–8 nm and modified with poly EGMP (ethylene glycol methacrylate phosphate) and N-Fluorescein Acrylamide was assessed.
• The dose of administration directly affecting the brain, liver, and spleen tissues distribution, retention, and uptake of YNPs and direct correlation between the absorbed amount and higher dose administered.
• YNPs can act as a potent direct antioxidant in a dose-dependent manner with good permeability through blood–brain barrier (BBB).
Graphical abstract
Yttrium oxide nanoparticles (Y 2 O 3 ) have been synthesized by a low temperature co-precipitation method. The precursor material used in this research was yttrium nitrate hexahydrate (as a basic material), ammonium hydroxide (as a precipitating agent) without surfactant. The resultant precipitate Y(OH) 3 was washed with deionized water several times and then heat treated at 450 °C for 1hr. The prepared Y 2 O 3 nanoparticles were characterized by TG-DTA, XRD, DLS, Zetasizer and TEM. From the results obtained, Y 2 O 3 ultrafine nanoparticles with particle size of 7.78 nm were successfully prepared as promise for wide range of applications.
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