Abstract
We report the development of potential theranostic agents for cardiovascular disease that are based on high-density lipoprotein-like magnetic nanostructures (HDL-MNS). The HDL-MNS offer prospects for diagnosis via noninvasive magnetic resonance imaging for anatomic detection and also serve as effective cholesterol efflux agents to address atherosclerotic vascular lesions. The HDL-MNS are synthesized by adding phospholipids and the HDL-defining apolipoprotein A1 to the surface of magnetic nanostructures (MNS) to mimic some aspects of natural HDL particles. From a diagnostic perspective, HDL-MNS show a 5 times higher contrast (r2 relaxivity up to 383 mM-1 s-1) in magnetic resonance imaging (MRI) than commercially available T2 MRI contrast agents (e.g., Ferumoxytol). Internalization of HDL-MNS by macrophage cells was confirmed by transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDX), inductive-coupled plasma mass spectrometry (ICP-MS), and successfully imaged via MRI. Also, the HDL-MNS particles show capacity to induce cholesterol efflux (∼4.8%) from macrophage cells comparable to natural HDL (∼4.7%), providing a pathway to prevent and treat cardiovascular disease via reverse cholesterol transport. The ability to image macrophage cells that have internalized HDL-MNS along with the cholesterol efflux capacity demonstrates the potential of the HDL-MNS particles as theranostic agents.
Original language | English (US) |
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Pages (from-to) | 2276-2282 |
Number of pages | 7 |
Journal | Chemistry of Materials |
Volume | 29 |
Issue number | 5 |
DOIs | |
State | Published - Mar 14 2017 |
Funding
The authors gratefully acknowledges support from the NTUNU Institute for NanoMedicine located at the International Institute for Nanotechnology, Northwestern University, USA and the Nanyang Technological University, Singapore. This work made use of the EPIC, Keck-II, and/or SPID facility(ies) of Northwestern University’s NUANCE Center, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205); the MRSEC program (NSF DMR-1121262) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IIN. Imaging work was performed at the Northwestern University Center for Advanced Molecular Imaging generously supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie omprehensive Cancer Center. J.S.R. is grateful for support from the NIH NHLBI Vascular Surgery Scientist Training Program (T32 HL094293).
ASJC Scopus subject areas
- General Chemistry
- General Chemical Engineering
- Materials Chemistry