title: Hierarchically-Structured Magnetic Nanoconstructs with Enhanced Relaxivity and Cooperative Tumor Accumulation.
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 (r2~ 835 (mM·s)-1) higher than conventional USPIOs and, under external magnetic fields, collectively cooperate to amplify tumor accumulation. The boost in r2relaxivity 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 consequent 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 animal) as compared to current practice.
authors.affiliation: Department of Translational Imaging and Department of Nanomedicine, The Methodist Hospital Research Institute, 6560 Fannin St, Houston, 77030, TX - USA. Department of Chemistry and the R.E. Smalley Institute for Nanoscale Science and Technology, Rice University, Houston, 77251-1892, TX - USA.
authors.forename: Ayrat
authors.initials: A
authors.lastname: Gizzatov
authors.affiliation: Department of Translational Imaging and Department of Nanomedicine, The Methodist Hospital Research Institute, 6560 Fannin St, Houston, 77030, TX - USA.
authors.forename: Jaehong
authors.initials: J
authors.lastname: Key
authors.affiliation: Department of Translational Imaging and Department of Nanomedicine, The Methodist Hospital Research Institute, 6560 Fannin St, Houston, 77030, TX - USA.
authors.forename: Santosh
authors.initials: S
authors.lastname: Aryal
authors.affiliation: Department of Translational Imaging and Department of Nanomedicine, The Methodist Hospital Research Institute, 6560 Fannin St, Houston, 77030, TX - USA.
authors.forename: Jeyarama
authors.initials: J
authors.lastname: Ananta
authors.affiliation: Department of Translational Imaging and Department of Nanomedicine, The Methodist Hospital Research Institute, 6560 Fannin St, Houston, 77030, TX - USA. Department of Mechanics, Politecnico di Torino, Corso Duca degli Abruzzi 24, Turin, 10129, IT.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cervadoro
authors.affiliation: Department of Translational Imaging and Department of Nanomedicine, The Methodist Hospital Research Institute, 6560 Fannin St, Houston, 77030, TX - USA. Department of Experimental and Clinical Medicine, University of Magna Graecia, Catanzaro, 88100, IT.
authors.forename: Anna Lisa
authors.initials: AL
authors.lastname: Palange
authors.affiliation: Department of Translational Imaging and Department of Nanomedicine, The Methodist Hospital Research Institute, 6560 Fannin St, Houston, 77030, TX - USA. Department of Energy, Politecnico di Torino, Corso Duca degli Abruzzi 24, Turin, 10129, IT.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fasano
authors.affiliation: Department of Translational Imaging and Department of Nanomedicine, The Methodist Hospital Research Institute, 6560 Fannin St, Houston, 77030, TX - USA. Department of Biosciences, Biotechnology and Pharmacological Sciences, University of Bari, Bari, 70126, IT.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Stigliano
authors.affiliation: Department of Translational Imaging and Department of Nanomedicine, The Methodist Hospital Research Institute, 6560 Fannin St, Houston, 77030, TX - USA.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhong
authors.affiliation: Department of Translational Imaging and Department of Nanomedicine, The Methodist Hospital Research Institute, 6560 Fannin St, Houston, 77030, TX - USA. Department of Experimental and Clinical Medicine, University of Magna Graecia, Catanzaro, 88100, IT.
authors.forename: Daniele
authors.initials: D
authors.lastname: Di Mascolo
authors.affiliation: Department of Chemistry and the R.E. Smalley Institute for Nanoscale Science and Technology, Rice University, Houston, 77251-1892, TX - USA.
authors.forename: Adem
authors.initials: A
authors.lastname: Guven
authors.affiliation: Department of Energy, Politecnico di Torino, Corso Duca degli Abruzzi 24, Turin, 10129, IT.
authors.forename: Eliodoro
authors.initials: E
authors.lastname: Chiavazzo
authors.affiliation: Department of Energy, Politecnico di Torino, Corso Duca degli Abruzzi 24, Turin, 10129, IT.
authors.forename: Pietro
authors.initials: P
authors.lastname: Asinari
authors.affiliation: Department of Translational Imaging and Department of Nanomedicine, The Methodist Hospital Research Institute, 6560 Fannin St, Houston, 77030, TX - USA.
authors.forename: Xuewu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Translational Imaging and Department of Nanomedicine, The Methodist Hospital Research Institute, 6560 Fannin St, Houston, 77030, TX - USA. Department of Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, 10065, NY - USA.
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
authors.affiliation: Department of Chemistry and the R.E. Smalley Institute for Nanoscale Science and Technology, Rice University, Houston, 77251-1892, TX - USA.
authors.forename: Lon J
authors.initials: LJ
authors.lastname: Wilson
authors.affiliation: Department of Translational Imaging and Department of Nanomedicine, The Methodist Hospital Research Institute, 6560 Fannin St, Houston, 77030, TX - USA. Department of Experimental and Clinical Medicine, University of Magna Graecia, Catanzaro, 88100, IT.
authors.forename: Paolo
authors.initials: P
authors.lastname: Decuzzi
keywords: MRI; magnetic guidance; magnetic nanoparticles; mesoporous matrices; relaxivity