Redoxable heteronanocrystals functioning magnetic relaxation switch for activatable T₁ and T₂ dual-mode magnetic resonance imaging

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• 作者：Myeong-Hoon Kim^a ; Hye-Young Son^b ; Ga-Yun Kim^a ; Kwangyeol Park^b ; Yong-Min Huh^b ; ^c ; ^{ymhuh@yuhs.ac" class="auth_mail" title="E-mail the corresponding author} ; Seungjoo Haam^a ; ^{haam@yonsei.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Magnetic nanoparticles ; Dual-mode contrast agent ; MR imaging ; Glutathione ; Stimuli-responsive
• 刊名：Biomaterials
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：101
• 期：Complete
• 页码：121-130
• 全文大小：2563 K

文摘

T₁/T₂ 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 T₁/T₂ 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 T₂ 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 T₁- and T₂-weighted MR imaging in tumor-bearing mice.