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Title: Complementary approaches for the evaluation of biocompatibility of 90Y-labeled superparamagnetic citric acid (Fe,Er) 3O 4 coated nanoparticles

Abstract

Magnetic nanoparticles (MNPs) are of immense interest for diagnostic and therapeutic applications in medicine. Design and development of new iron oxide-based MNPs for such applications is of rather limited breadth without reliable and sensitive methods to determine their levels in body tissues. Commonly used methods, such as ICP, are quite problematic, due to the inability to decipher the origin of the detected iron, i.e. whether it originates from the MNPs or endogenous from tissues and bodily fluids. One of the approaches to overcome this problem and to increase reliability of tracing MNPs is to partially substitute iron ions in the MNPs with Er. Here, we report on the development of citric acid coated (Fe,Er) 3O 4 nanoparticles and characterization of their physico-chemical and biological properties by utilization of various complementary approaches. The synthesized MNPs had a narrow (6–7 nm) size distribution, as consistently seen in atomic pair distribution function, transmission electron microscopy, and DC magnetization measurements. The particles were found to be superparamagnetic, with a pronounced maximum in measured zero-field cooled magnetization at around 90 K. Reduction in saturation magnetization due to incorporation of 1.7% Er 3+ into the Fe 3O 4 matrix was clearly observed. From the biological standpoint,more » citric acid coated (Fe,Er) 3O 4 NPs were found to induce low toxicity both in human cell fibroblasts and in zebrafish ( Danio rerio) embryos. Biodistribution pattern of the MNPs after intravenous administration in healthy Wistar rats was followed by the radiotracer method, revealing that 90Y-labeled MNPs were predominantly found in liver (75.33% ID), followed by lungs (16.70% ID) and spleen (2.83% ID). Quantitative agreement with these observations was obtained by ICP-MS elemental analysis using Er as the detected tracer. Based on the favorable physical, chemical and biological characteristics, citric acid coated (Fe,Er) 3O 4 MNPs could be further considered for the potential application as a diagnostic and/or therapeutic agent. Lastly, this work also demonstrates that combined application of these techniques is a promising tool for studies of pharmacokinetics of the new MNPs in complex biological systems.« less

Authors:
 [1];  [1];  [1];  [2];  [2];  [3];  [1];  [1];  [1]
  1. Univ. of Belgrade, Belgrade (Serbia)
  2. Beijing Univ. of Technology, Beijing (People's Republic of China)
  3. Brookhaven National Lab. (BNL), Upton, NY (United States)
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1345741
Report Number(s):
BNL-113583-2017-JA
Journal ID: ISSN 0928-4931; R&D Project: PO011; KC0201060; TRN: US1700864
Grant/Contract Number:
SC00112704
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Materials Science and Engineering. C, Biomimetic Materials, Sensors and Systems
Additional Journal Information:
Journal Volume: 75; Journal Issue: C; Journal ID: ISSN 0928-4931
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; magnetic nanoparticle; biodistribution; embryotoxicity; radiolabeling; MNP

Citation Formats

Antic, Bratislav, Boskovic, Marko, Nikodinovic-Runic, Jasmina, Ming, Yue, Zhang, Hongguo, Bozin, Emil S., Jankovic, Drina, Spasojevic, Vojislav, and Vranjes-Djuric, Sanja. Complementary approaches for the evaluation of biocompatibility of 90Y-labeled superparamagnetic citric acid (Fe,Er)3O4 coated nanoparticles. United States: N. p., 2017. Web. doi:10.1016/j.msec.2017.02.023.
Antic, Bratislav, Boskovic, Marko, Nikodinovic-Runic, Jasmina, Ming, Yue, Zhang, Hongguo, Bozin, Emil S., Jankovic, Drina, Spasojevic, Vojislav, & Vranjes-Djuric, Sanja. Complementary approaches for the evaluation of biocompatibility of 90Y-labeled superparamagnetic citric acid (Fe,Er)3O4 coated nanoparticles. United States. doi:10.1016/j.msec.2017.02.023.
Antic, Bratislav, Boskovic, Marko, Nikodinovic-Runic, Jasmina, Ming, Yue, Zhang, Hongguo, Bozin, Emil S., Jankovic, Drina, Spasojevic, Vojislav, and Vranjes-Djuric, Sanja. Fri . "Complementary approaches for the evaluation of biocompatibility of 90Y-labeled superparamagnetic citric acid (Fe,Er)3O4 coated nanoparticles". United States. doi:10.1016/j.msec.2017.02.023. https://www.osti.gov/servlets/purl/1345741.
@article{osti_1345741,
title = {Complementary approaches for the evaluation of biocompatibility of 90Y-labeled superparamagnetic citric acid (Fe,Er)3O4 coated nanoparticles},
author = {Antic, Bratislav and Boskovic, Marko and Nikodinovic-Runic, Jasmina and Ming, Yue and Zhang, Hongguo and Bozin, Emil S. and Jankovic, Drina and Spasojevic, Vojislav and Vranjes-Djuric, Sanja},
abstractNote = {Magnetic nanoparticles (MNPs) are of immense interest for diagnostic and therapeutic applications in medicine. Design and development of new iron oxide-based MNPs for such applications is of rather limited breadth without reliable and sensitive methods to determine their levels in body tissues. Commonly used methods, such as ICP, are quite problematic, due to the inability to decipher the origin of the detected iron, i.e. whether it originates from the MNPs or endogenous from tissues and bodily fluids. One of the approaches to overcome this problem and to increase reliability of tracing MNPs is to partially substitute iron ions in the MNPs with Er. Here, we report on the development of citric acid coated (Fe,Er)3O4 nanoparticles and characterization of their physico-chemical and biological properties by utilization of various complementary approaches. The synthesized MNPs had a narrow (6–7 nm) size distribution, as consistently seen in atomic pair distribution function, transmission electron microscopy, and DC magnetization measurements. The particles were found to be superparamagnetic, with a pronounced maximum in measured zero-field cooled magnetization at around 90 K. Reduction in saturation magnetization due to incorporation of 1.7% Er3+ into the Fe3O4 matrix was clearly observed. From the biological standpoint, citric acid coated (Fe,Er)3O4 NPs were found to induce low toxicity both in human cell fibroblasts and in zebrafish (Danio rerio) embryos. Biodistribution pattern of the MNPs after intravenous administration in healthy Wistar rats was followed by the radiotracer method, revealing that 90Y-labeled MNPs were predominantly found in liver (75.33% ID), followed by lungs (16.70% ID) and spleen (2.83% ID). Quantitative agreement with these observations was obtained by ICP-MS elemental analysis using Er as the detected tracer. Based on the favorable physical, chemical and biological characteristics, citric acid coated (Fe,Er)3O4 MNPs could be further considered for the potential application as a diagnostic and/or therapeutic agent. Lastly, this work also demonstrates that combined application of these techniques is a promising tool for studies of pharmacokinetics of the new MNPs in complex biological systems.},
doi = {10.1016/j.msec.2017.02.023},
journal = {Materials Science and Engineering. C, Biomimetic Materials, Sensors and Systems},
number = C,
volume = 75,
place = {United States},
year = {Fri Feb 10 00:00:00 EST 2017},
month = {Fri Feb 10 00:00:00 EST 2017}
}

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  • This study describes the distribution of intravenously injected polyacrylic acid (PAA) coated γ-Fe{sub 2}O{sub 3} NPs (10 mg kg{sup −1}) at the organ, cellular and subcellular levels in healthy BALB/cJ mice and in parallel addresses the effects of NP injection on kidney function, blood pressure and vascular contractility. Magnetic resonance imaging (MRI) and transmission electron microscopy (TEM) showed accumulation of NPs in the liver within 1 h after intravenous infusion, accommodated by intracellular uptake in endothelial and Kupffer cells with subsequent intracellular uptake in renal cells, particularly the cytoplasm of the proximal tubule, in podocytes and mesangial cells. The renofunctionalmore » effects of NPs were evaluated by arterial acid–base status and measurements of glomerular filtration rate (GFR) after instrumentation with chronically indwelling catheters. Arterial pH was 7.46 ± 0.02 and 7.41 ± 0.02 in mice 0.5 h after injections of saline or NP, and did not change over the next 12 h. In addition, the injections of NP did not affect arterial PCO{sub 2} or [HCO{sub 3}{sup −}] either. Twenty-four and 96 h after NP injections, the GFR averaged 0.35 ± 0.04 and 0.35 ± 0.01 ml min{sup −1} g{sup −1}, respectively, values which were statistically comparable with controls (0.29 ± 0.02 and 0.33 ± 0.1 ml{sup –1} min{sup –1} 25 g{sup –1}). Mean arterial blood pressure (MAP) decreased 12–24 h after NP injections (111.1 ± 11.5 vs 123.0 ± 6.1 min{sup −1}) associated with a decreased contractility of small mesenteric arteries revealed by myography to characterize endothelial function. In conclusion, our study demonstrates that accumulation of superparamagnetic iron oxide nanoparticles does not affect kidney function in healthy mice but temporarily decreases blood pressure. -- Highlights: ► PAA coated γ-Fe{sub 2}O{sub 3} nanoparticles were injected intravenously into healthy mice. ► We examine the distribution and physiological effects of nanoparticle accumulation. ► No effects of accumulation in kidney on acid-base status or GFR. ► Acute hypotension associated with decreased contractility of small vessels. ► We demonstrate physiological effects of PAA γ-Fe{sub 2}O{sub 3} NP for medical purposes.« less
  • Highlights: ► Heptanoic acid@Fe{sub 3}O{sub 4} nanocomposite has been prepared via simple polyol. ► Heptanoic acid used as both surfactant and solvents. ► Magneto polymer composite with adjustable Ea has a potential usage as functional composites. - Abstract: Magnetite (Fe{sub 3}O{sub 4}) nanoparticles were prepared via polyol method by using FeCl{sub 2} as only source of iron. As-prepared samples were characterized by powder X-ray diffractometer (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), thermal gravimetric analyzer (TGA) and vibrating sample magnetometer (VSM). Crystalline phase was identified as Fe{sub 3}O{sub 4} and the crystallite sizes were calculated as 19.1more » ± 1.1 and 22 ± 1.3 nm for uncalcinated and calcinated products from X-ray line profile fitting. The capping of heptanoic acid around Fe{sub 3}O{sub 4} nanoparticles was confirmed by FT-IR spectroscopy, the interaction being via bridging oxygen's of the carboxylate and the nanoparticle surface and also by TG analysis. VSM measurements showed that both samples exhibited typical superparamagnetic behavior at room temperature with different Ms values. The ε′ decreases with increasing frequency for both composites and permeability has almost same values for all temperatures at higher frequencies. As synthesized and calcinated samples conductivity increase linearly with the temperature.« less
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