Journal
BIOMATERIALS
Volume 101, Issue -, Pages 121-130Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2016.05.054
Keywords
Magnetic nanoparticles; Dual-mode contrast agent; MR imaging; Glutathione; Stimuli-responsive
Funding
- Bio & Medical Technology Development Program of the National Research Foundation (NRF) - Korean government (MEST) [2012050077]
- Bio & Medical Technology Development Program of the National Research Foundation (NRF) - Ministry of Science, ICT & Future Planning [NRF-2015M3A9D7029878]
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T-1/T-2 dual-mode magnetic resonance (MR) contrast agents (DMCAs) have gained much attention because of their ability to improve accuracy by providing two pieces of complementary information with one instrument. However, most of these agents are always ON systems that emit MR contrast regardless of their interaction with target cells or biomarkers, which may result in poor target-to-background ratios. Herein, we introduce a rationally designed magnetic relaxation switch (MGRS) for an activatable T-1/T-2 dual MR imaging system. Redox-responsive heteronanocrystals, consisting of a superparamagnetic Fe3O4 core and a paramagnetic Mn3O4 shell, are synthesized through seed-mediated growth and subsequently surface-modified with polysorbate 80. The Mn3O4 shell acts as both a protector of Fe3O4 in aqueous environments to attenuate T-2 relaxation and as a redoxable switch that can be activated in intracellular reducing environments by glutathione. This simultaneously generates large amounts of magnetically decoupled Mn2+ ions and allows Fe3O4 to interact with the water protons. This smart nanoplatform shows an appropriate hydrodynamic size for the EPR effect (10-100 nm) and demonstrates biocompatibility. Efficient transitions of OFF/ON dual contrast effects are observed by in vitro imaging and MR relaxivity measurements. The ability to use these materials as DMCAs is demonstrated via effective passive tumor targeting for T-1- and T-2-weighted MR imaging in tumor-bearing mice. (C) 2016 Elsevier Ltd. All rights reserved.
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