title: Geometrical confinement of Gd(DOTA) molecules within mesoporous silicon nanoconstructs for MR imaging of cancer.
abstract: Porous silicon has been used for the delivery of therapeutic and imaging agents in several biomedical applications. Here, mesoporous silicon nanoconstructs (SiMPs) with a discoidal shape and a sub-micrometer size (1000×400nm) have been conjugated with gadolinium-tetraazacyclododecane tetraacetic acid Gd(DOTA) molecules and proposed as contrast agents for Magnetic Resonance Imaging. The surface of the SiMPs with different porosities - small pore (SP: ∼5nm) and huge pore (HP: ∼40nm) - and of bulk, non-porous silica beads (1000nm in diameter) have been modified with covalently attached (3-aminopropyl)triethoxysilane (APTES) groups, conjugated with DOTA molecules, and reacted with an aqueous solution of GdCl3. The resulting Gd(DOTA) molecules confined within the small pores of the Gd-SiMPs achieve longitudinal relaxivities r1 of ∼17 (mMs)(-)(1), which is 4 times greater than for free Gd(DOTA). This enhancement is ascribed to the confinement and stable chelation of Gd(DOTA) molecules within the SiMP mesoporous matrix. The resulting nanoconstructs possess no cytotoxicity and accumulate in ovarian tumors up to 2% of the injected dose per gram tissue, upon tail vein injection. All together this data suggests that Gd-SiMPs could be efficiently used for MR vascular imaging in cancer and other diseases.
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: 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: Jeyerama S
authors.initials: JS
authors.lastname: Ananta
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: Richa
authors.initials: R
authors.lastname: Sethi
authors.affiliation: Department of Translational Imaging and Department of Nanomedicine, The Methodist Hospital Research Institute, 6560 Fannin St, Houston, 77030 TX, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Xu
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 Translational Imaging and Department of Nanomedicine, The Methodist Hospital Research Institute, 6560 Fannin St, Houston, 77030 TX, USA.
authors.forename: Maricela
authors.initials: M
authors.lastname: Ramirez
authors.affiliation: Department of Translational Imaging and Department of Nanomedicine, The Methodist Hospital Research Institute, 6560 Fannin St, Houston, 77030 TX, USA.
authors.forename: Haifa
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, 77030 TX, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Sood
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.
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. Electronic address: pdecuzzi@houstonmethodist.org.
authors.forename: Paolo
authors.initials: P
authors.lastname: Decuzzi
mesh_terms: D003287:Contrast Media / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D008279:Magnetic Resonance Imaging; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000175:diagnosis*; D009942:Organometallic Compounds / Q000737:chemistry*; D016062:Porosity; D012825:Silicon / Q000737:chemistry*
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; D012825:Silicon
keywords: Magnetic Resonance Imaging; Mesoporous silicon; Nanoconstructs; Relaxivity