Geometrical confinement of Gd(DOTA) molecules within mesoporous silicon nanoconstructs for MR imaging of cancer

Ayrat Gizzatov; Cinzia Stigliano; Jeyerama S Ananta; Richa Sethi; Rong Xu; Adem Guven; Maricela Ramirez; Haifa Shen; Anil Sood; Mauro Ferrari; Lon J Wilson; Xuewu Liu; Paolo Decuzzi

doi:10.1016/j.canlet.2014.06.001

Geometrical confinement of Gd(DOTA) molecules within mesoporous silicon nanoconstructs for MR imaging of cancer

Cancer Lett. 2014 Sep 28;352(1):97-101. doi: 10.1016/j.canlet.2014.06.001. Epub 2014 Jun 12.

Authors

Affiliations

¹ 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.
² Department of Translational Imaging and Department of Nanomedicine, The Methodist Hospital Research Institute, 6560 Fannin St, Houston, 77030 TX, USA.
³ Department of Chemistry and the R.E. Smalley Institute for Nanoscale Science and Technology, Rice University, Houston, 77251-1892 TX, USA.
⁴ Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, 77030 TX, USA.
⁵ 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.
⁶ 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.

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.

Keywords: Magnetic Resonance Imaging; Mesoporous silicon; Nanoconstructs; Relaxivity.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Contrast Media / chemistry*
Heterocyclic Compounds / chemistry*
Humans
Magnetic Resonance Imaging*
Molecular Structure
Nanoparticles / chemistry*
Neoplasms / diagnosis*
Organometallic Compounds / chemistry*
Porosity
Silicon / chemistry*

Substances

Contrast Media
Heterocyclic Compounds
Organometallic Compounds
gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
Silicon

Abstract

Publication types

MeSH terms

Substances

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