Hierarchically Structured Magnetic Nanoconstructs with Enhanced Relaxivity and Cooperative Tumor Accumulation |
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Authors: | Ayrat Gizzatov Jaehong Key Santosh Aryal Jeyarama Ananta Antonio Cervadoro Anna Lisa Palange Matteo Fasano Cinzia Stigliano Meng Zhong Daniele Di Mascolo Adem Guven Eliodoro Chiavazzo Pietro Asinari Xuewu Liu Mauro Ferrari Lon J Wilson Paolo Decuzzi |
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Institution: | 1. Department of Translational Imaging and Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, TX, USA;2. Department of Chemistry and the R.E. Smalley Institute for Nanoscale Science and Technology, Rice University, Houston, TX, USA;3. Department of Mechanics, Politecnico di Torino, Turin, IT;4. Department of Experimental and Clinical Medicine, University of Magna Graecia, Catanzaro, IT;5. Department of Energy, Politecnico di Torino, Turin, IT;6. Department of Biosciences, Biotechnology and Pharmacological Sciences, University of Bari, Bari, IT;7. Department of Medicine, Weill Cornell Medical College, New York, NY, USA |
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Abstract: | Iron oxide nanoparticles are formidable multifunctional systems capable of contrast enhancement in magnetic resonance imaging, guidance under remote fields, heat generation, and biodegradation. Yet, this potential is underutilized in that each function manifests at different nanoparticle sizes. Here, sub‐micrometer discoidal magnetic nanoconstructs are realized by confining 5 nm ultra‐small super‐paramagnetic iron oxide nanoparticles (USPIOs) within two different mesoporous structures, made out of silicon and polymers. These nanoconstructs exhibit transversal relaxivities up to ≈10 times (r 2 ≈ 835 mm ?1 s?1) higher than conventional USPIOs and, under external magnetic fields, collectively cooperate to amplify tumor accumulation. The boost in r 2 relaxivity arises from the formation of mesoscopic USPIO clusters within the porous matrix, inducing a local reduction in water molecule mobility as demonstrated via molecular dynamics simulations. The cooperative accumulation under static magnetic field derives from the large amount of iron that can be loaded per nanoconstuct (up to ≈65 fg) and the consequential generation of significant inter‐particle magnetic dipole interactions. In tumor bearing mice, the silicon‐based nanoconstructs provide MRI contrast enhancement at much smaller doses of iron (≈0.5 mg of Fe kg?1 animal) as compared to current practice. |
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Keywords: | MRI magnetic nanoparticles magnetic guidance relaxivity mesoporous matrices |
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