Gadolinium-Encapsulating Iron Oxide Nanoprobe as Activatable NMR/MRI Contrast Agent
- 18 July 2012
- journal article
- research article
- Published by American Chemical Society (ACS) in ACS Nano
- Vol. 6 (8), 7281-7294
- https://doi.org/10.1021/nn302393e
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 (T1). Upon release of the Gd-DTPA complex from the nanoprobe’s polymeric coating in acidic media, an increase in the T1 relaxation rate (1/T1) of the composite magnetic nanoprobe was observed, indicating a dequenching of the nanoprobe with a corresponding increase in the T1-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/T1 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 T1 activation. In addition, when an anticancer drug (Taxol) was coencapsulated with the Gd-DTPA within the folate receptor targeting composite magnetic nanoprobe, the T1 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 T1 nanoagent could be of great importance for the detection of acidic tumors and assessment of drug targeting and release by MRI.This publication has 69 references indexed in Scilit:
- Receptor-targeted iron oxide nanoparticles for molecular MR imaging of inflamed atherosclerotic plaquesBiomaterials, 2011
- Activatable T 1 and T 2 Magnetic Resonance Imaging Contrast AgentsAnnals of Biomedical Engineering, 2011
- Synthesis and Characterization of New Porphyrazine-Gd(III) Conjugates as Multimodal MR Contrast AgentsBioconjugate Chemistry, 2010
- Gadolinium‐Conjugated Dendrimer Nanoclusters as a Tumor‐Targeted T1 Magnetic Resonance Imaging Contrast AgentAngewandte Chemie, 2009
- Porous Polymersomes with Encapsulated Gd‐Labeled Dendrimers as Highly Efficient MRI Contrast AgentsAdvanced Functional Materials, 2009
- Multimodal Gadolinium‐Enriched DNA–Gold Nanoparticle Conjugates for Cellular ImagingAngewandte Chemie, 2009
- Drug/Dye‐Loaded, Multifunctional Iron Oxide Nanoparticles for Combined Targeted Cancer Therapy and Dual Optical/Magnetic Resonance ImagingSmall, 2009
- Bioresponsive, Cell-Penetrating, and Multimeric MR Contrast AgentsAccounts of Chemical Research, 2009
- Oxidase‐Like Activity of Polymer‐Coated Cerium Oxide NanoparticlesAngewandte Chemie-International Edition, 2009
- Cell-Permeable MR Contrast Agents with Increased Intracellular RetentionBioconjugate Chemistry, 2008