Gadolinium-encapsulating iron oxide nanoprobe as activatable NMR/MRI contrast agent Journal Article


Authors: Santra, S.; Jativa, S. D.; Kaittanis, C.; Normand, G.; Grimm, J.; Perez, J. M.
Article Title: Gadolinium-encapsulating iron oxide nanoprobe as activatable NMR/MRI contrast agent
Abstract: Herein we report a novel gadolinium-encapsulating iron oxide nanoparticle-based activatable NMR/MRI nanoprobe. In our design, Gd-DTPA is encapsulated within the poly(acrylic acid) (PAA) polymer coating of a superparamagnetic iron oxide nanoparticle (IO-PAA), yielding a composite magnetic nanoprobe (IO-PAA-Gd-DTPA) with quenched longitudinal spin-lattice magnetic relaxation (T 1). Upon release of the Gd-DTPA complex from the nanoprobe's polymeric coating in acidic media, an increase in the T 1 relaxation rate (1/T 1) of the composite magnetic nanoprobe was observed, indicating a dequenching of the nanoprobe with a corresponding increase in the T 1-weighted MRI signal. When a folate-conjugated nanoprobe was incubated in HeLa cells, a cancer cell line overexpressing folate receptors, an increase in the 1/T 1 signal was observed. This result suggests that, upon receptor-mediated internalization, the composite magnetic nanoprobe degraded within the cell's lysosome acidic (pH 5.0) environment, resulting in an intracellular release of Gd-DTPA complex with subsequent T 1 activation. In addition, when an anticancer drug (Taxol) was coencapsulated with the Gd-DTPA within the folate receptor targeting composite magnetic nanoprobe, the T 1 activation of the probe coincided with the rate of drug release and corresponding cytotoxic effect in cell culture studies. Taken together, these results suggest that our activatable T 1 nanoagent could be of great importance for the detection of acidic tumors and assessment of drug targeting and release by MRI. © 2012 American Chemical Society.
Keywords: gadolinium; nuclear magnetic resonance imaging; methodology; magnetic resonance imaging; cytology; cell line; cytotoxicity; hela cell; hela cells; chemistry; diagnostic agent; cell culture; magnetic resonance spectroscopy; nuclear magnetic resonance spectroscopy; contrast medium; contrast media; heart muscle cell; contrast agent; synthesis; carboxylic acids; anticancer drug; iron oxides; metal nanoparticles; drug release; folate receptor; myocytes, cardiac; nanocapsule; cancer cell lines; gd-dtpa; activatable mri imaging; gd-dtpa complex; iron oxide nanoprobe; magnetic relaxation; theranostic application; acidic media; cytotoxic effects; dequenching; drug-targeting; polyacrylic acids; polymer coating; polymeric coatings; relaxation rates; spin lattices; superparamagnetic iron oxide nanoparticles; coatings; signal systems; superparamagnetism; nanoprobes; magnetite nanoparticle; magnetite nanoparticles; nanocapsules
Journal Title: ACS Nano
Volume: 6
Issue: 8
ISSN: 1936-0851
Publisher: American Chemical Society  
Date Published: 2012-08-28
Start Page: 7281
End Page: 7294
Language: English
DOI: 10.1021/nn302393e
PROVIDER: scopus
PMCID: PMC3429787
PUBMED: 22809405
DOI/URL:
Notes: --- - "Export Date: 1 October 2012" - "Source: Scopus"
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  1. Jan Grimm
    93 Grimm