Gadolinium-Encapsulating Iron Oxide Nanoprobe as Activatable NMR/MRI Contrast Agent

    Authors

    S. Santra; S. D. Jativa; C. Kaittanis; G. Normand; J. Grimm;J. M. Perez

    Comments

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    Abbreviated Journal Title

    ACS Nano

    Keywords

    activatable MRI imaging; magnetic relaxation; iron oxide nanoprobe; Gd-DTPA complex; theranostic application; MRI; NANOPARTICLES; RELAXATION; T-1; RELAXIVITY; COMPLEX; NANOCOMPOSITES; VISUALIZATION; ENHANCEMENT; SENSITIVITY; Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &; Nanotechnology; Materials Science, Multidisciplinary

    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.

    Journal Title

    Acs Nano

    Volume

    6

    Issue/Number

    8

    Publication Date

    1-1-2012

    Document Type

    Article

    Language

    English

    First Page

    7281

    Last Page

    7294

    WOS Identifier

    WOS:000307988900088

    ISSN

    1936-0851

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