Physical characterization and  in vivo  organ distribution of coated iron oxide nanoparticles

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Abstract

Citrate-stabilized iron oxide magnetic nanoparticles (MNPs) were coated with one of carboxymethyl dextran (CM-dextran), polyethylene glycol-polyethylene imine (PEG-PEI), methoxy-PEG-phosphate+rutin, or dextran. They were characterized for size, zeta potential, hysteresis heating in an alternating magnetic field, dynamic magnetic susceptibility, and examined for their distribution in mouse organs following intravenous delivery. Except for PEG-PEI-coated nanoparticles, all coated nanoparticles had a negative zeta potential at physiological pH. Nanoparticle sizing by dynamic light scattering revealed an increased nanoparticle hydrodynamic diameter upon coating. Magnetic hysteresis heating changed little with coating; however, the larger particles demonstrated significant shifts of the peak of complex magnetic susceptibility to lower frequency. 48 hours following intravenous injection of nanoparticles, mice were sacrificed and tissues were collected to measure iron concentration. Iron deposition from nanoparticles possessing a negative surface potential was observed to have highest accumulation in livers and spleens. In contrast, iron deposition from positively charged PEG-PEI-coated nanoparticles was observed to have highest concentration in lungs. These preliminary results suggest a complex interplay between nanoparticle size and charge determines organ distribution of systemically-delivered iron oxide magnetic nanoparticles.

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Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts.

Martin Lundqvist, Johannes Stigler, Giuliano Elia … (2008)

Nanoparticles in a biological fluid (plasma, or otherwise) associate with a range of biopolymers, especially proteins, organized into the "protein corona" that is associated with the nanoparticle and continuously exchanging with the proteins in the environment. Methodologies to determine the corona and to understand its dependence on nanomaterial properties are likely to become important in bionanoscience. Here, we study the long-lived ("hard") protein corona formed from human plasma for a range of nanoparticles that differ in surface properties and size. Six different polystyrene nanoparticles were studied: three different surface chemistries (plain PS, carboxyl-modified, and amine-modified) and two sizes of each (50 and 100 nm), enabling us to perform systematic studies of the effect of surface properties and size on the detailed protein coronas. Proteins in the corona that are conserved and unique across the nanoparticle types were identified and classified according to the protein functional properties. Remarkably, both size and surface properties were found to play a very significant role in determining the nanoparticle coronas on the different particles of identical materials. We comment on the future need for scientific understanding, characterization, and possibly some additional emphasis on standards for the surfaces of nanoparticles.

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Toxicity of nanomaterials.

Shahriar Sharifi, Shahed Behzadi, Sophie Laurent … (2012)

Nanoscience has matured significantly during the last decade as it has transitioned from bench top science to applied technology. Presently, nanomaterials are used in a wide variety of commercial products such as electronic components, sports equipment, sun creams and biomedical applications. There are few studies of the long-term consequences of nanoparticles on human health, but governmental agencies, including the United States National Institute for Occupational Safety and Health and Japan's Ministry of Health, have recently raised the question of whether seemingly innocuous materials such as carbon-based nanotubes should be treated with the same caution afforded known carcinogens such as asbestos. Since nanomaterials are increasing a part of everyday consumer products, manufacturing processes, and medical products, it is imperative that both workers and end-users be protected from inhalation of potentially toxic NPs. It also suggests that NPs may need to be sequestered into products so that the NPs are not released into the atmosphere during the product's life or during recycling. Further, non-inhalation routes of NP absorption, including dermal and medical injectables, must be studied in order to understand possible toxic effects. Fewer studies to date have addressed whether the body can eventually eliminate nanomaterials to prevent particle build-up in tissues or organs. This critical review discusses the biophysicochemical properties of various nanomaterials with emphasis on currently available toxicology data and methodologies for evaluating nanoparticle toxicity (286 references).

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Long-circulating and target-specific nanoparticles: theory to practice.

S M Moghimi, A C Hunter, J C Murray (2001)

The rapid recognition of intravenously injected colloidal carriers, such as liposomes and polymeric nanospheres from the blood by Kupffer cells, has initiated a surge of development for "Kupffer cell-evading" or long-circulating particles. Such carriers have applications in vascular drug delivery and release, site-specific targeting (passive as well as active targeting), as well as transfusion medicine. In this article we have critically reviewed and assessed the rational approaches in the design as well as the biological performance of such constructs. For engineering and design of long-circulating carriers, we have taken a lead from nature. Here, we have explored the surface mechanisms, which affords red blood cells long-circulatory lives and the ability of specific microorganisms to evade macrophage recognition. Our analysis is then centered where such strategies have been translated and fabricated to design a wide range of particulate carriers (e.g., nanospheres, liposomes, micelles, oil-in-water emulsions) with prolonged circulation and/or target specificity. With regard to the targeting issues, attention is particularly focused on the importance of physiological barriers and disease states.

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Author and article information

Contributors

Robert Ivkov: rivkov1@jhmi.edu

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 20 March 2018

Publication date PMC-release: 20 March 2018

Publication date Collection: 2018

Volume: 8

Electronic Location Identifier: 4916

Affiliations

[1 ]Johns Hopkins University School of Medicine, Department of Radiation Oncology and Molecular Radiation Sciences, 1550 Orleans Street, CRB II, Baltimore, MD 21231 USA

[2 ]Micromod Partikeltechnologie GmbH, Friedrich-Barnewitz-St 4, D-18119 Rostock, Germany

[3 ]ISNI 0000 0001 2171 9311, GRID grid.21107.35, Johns Hopkins Bloomberg School of Public Health, , Department of Environmental Health Sciences, ; Baltimore, MD 21205 USA

[4 ]ISNI 0000 0001 2171 9311, GRID grid.21107.35, Department of Mechanical Engineering, Whiting School of Engineering, , Johns Hopkins University, ; Baltimore, 21218 USA USA

[5 ]ISNI 0000 0001 2171 9311, GRID grid.21107.35, Department of Oncology, Sidney Kimmel Comprehensive Cancer Centre, School of Medicine, , Johns Hopkins University, ; Baltimore, MD 21231 USA

[6 ]ISNI 0000 0001 2171 9311, GRID grid.21107.35, Department of Materials Science and Engineering, Whiting School of Engineering, , Johns Hopkins University, ; Baltimore, 21218 USA

[7 ]ISNI 0000 0001 2171 9311, GRID grid.21107.35, Institute for NanoBioTechnology, Whiting School of Engineering, , Johns Hopkins University, ; Baltimore, 21218 USA

Article

Publisher ID: 23317

DOI: 10.1038/s41598-018-23317-2

PMC ID: 5861066

PubMed ID: 29559734

SO-VID: 884f8334-3129-4ff6-9600-4b89e982005c

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 4 December 2017

Date accepted : 9 March 2018

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Physical characterization and in vivo organ distribution of coated iron oxide nanoparticles

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Most cited references 47

Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts.

Toxicity of nanomaterials.

Long-circulating and target-specific nanoparticles: theory to practice.

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Cited by 22

Most referenced authors 967