Cardiovascular “Eat-Me” Imaging

We develop and test new nanoparticles agents, which are tiny devices engineered to target cardiovascular disease while avoiding healthy tissues and organs. We engineer nanoparticle probes that selectively accumulate in atherosclerosis (a condition leading to heart disease), avoiding healthy organs and tissues, and significantly reducing dangerous side effects.

Our science was inspired by an intrinsic, naturally occurred mechanism by which ‘unwanted’ cells are removed by the organism. Our approach is to target macrophages, the cells found in large numbers at the sites of atherosclerosis, with nanoprobes that display “eat-me” signals. These “eat-me” signals are normally found on the surface of apoptotic (i.e., dying) cells, which are cleared rapidly by macrophages. When our nano-probes are injected, they get recognized by macrophages, engulfed, and retained at sites of disease. Nanoparticles that carry imaging probes, such as Gadolinium or a fluorescence label, “broadcast” their location in targeted cells through MRI or fluorescence imaging. Often in atherosclerosis, a macrophage engulfs an apoptotic cell and releases inflammatory signaling molecules that can be detrimental. “Eat-me” nanoparticles compete with apoptotic cells, and, when engulfed by macrophages, are able to deliver anti-inflammatory therapeutics. See more in our Drug Delivery projects.

Imaging macrophages through atherosclerosis-directed probes based on “eat-me” signaling opens new possibilities for non-antigenic targeting of nanomedicines. Such drug- and imaging probe-delivery approaches are expected to have lower cost than their antibody-based analogs and to circumvent the obstacles associated with many biologics, such as immunogenicity (for proteins) and mutagenicity (for viral vectors).

“Eat-me” agents can be used image (MRI) plaque deposits in atherosclerosis, retaining in aorta up to 24 hours after injection (arrows and zoom insets on figure below). Because most of the circulating agent is eliminated from the bloodstream after 24 hours, this imaging allows for a high contrast-to-noise ratio (CNR) signal in the plaque.

Imaging of mouse atherosclerosis (plaque deposit in abdominal aorta) using “eat-me” nanoparticles. Enhancement of aorta can be seen at 24 h after injection with high CNR.

We Published These!

• Bagalkot V, Deiuliis JA, Rajagopalan S, Maiseyeu A. “Eat me” imaging and therapy. Adv Drug Deliv Rev. 2016;99:2–11. 
• Maiseyeu A. Non-antigenic regulators of targeting for imaging and therapy. Adv Drug Deliv Rev. 2016;99:1. 
• Bagalkot V, Badgeley MA, Kampfrath T, Deiuliis JA, Rajagopalan S, Maiseyeu A. Hybrid nanoparticles improve targeting to inflammatory macrophages through phagocytic signals. J Control Release. 2015;217:243–255.
• Maiseyeu A, Bagalkot V. In vitro uptake of apoptotic body mimicking phosphatidylserine-quantum dot micelles by monocytic cell line. Nanoscale Res Lett. 2014;9:176. 
• Deiuliis J, Mihai G, Zhang J, Taslim C, Varghese JJ, Maiseyeu A, Huang K, Rajagopalan S. Renin-sensitive microRNAs correlate with atherosclerosis plaque progression. J Hum Hypertens. 2014;28:251–258.
• Giri S, Xue H, Maiseyeu A, Kroeker R, Rajagopalan S, White RD, Zuehlsdorff S, Raman SV, Simonetti OP. Steady-state first-pass perfusion (SSFPP): a new approach to 3D first-pass myocardial perfusion imaging. Magn Reson Med. 2014;71:133–144.  
• Sharkey-Toppen TP, Mihai G, Maiseyeu A, Tran T, Clymer BD, Simonetti OP, Raman SV. Improved in vivo human carotid artery wall T₂ estimation. Magn Reson Imaging. 2013;31:44–52. 
• Mihai G, Varghese J, Kampfrath T, Gushchina L, Hafer L, Deiuliis J, Maiseyeu A, Simonetti OP, Lu B, Rajagopalan S. Aliskiren effect on plaque progression in established atherosclerosis using high resolution 3D MRI (ALPINE): a double-blind placebo-controlled trial. J Am Heart Assoc. 2013;2:e004879.  
• Yang F, Zhang X, Maiseyeu A, Mihai G, Yasmeen R, DiSilvestro D, Maurya SK, Periasamy M, Bergdall KV, Duester G, Sen CK, Roy S, Lee LJ, Rajagopalan S, Ziouzenkova O. The prolonged survival of fibroblasts with forced lipid catabolism in visceral fat following encapsulation in alginate-poly-L-lysine. Biomaterials. 2012;33:5638–5649. 
• Maiseyeu A, Badgeley MA, Kampfrath T, Mihai G, Deiuliis JA, Liu C, Sun Q, Parthasarathy S, Simon DI, Croce K, Rajagopalan S. In vivo targeting of inflammation-associated myeloid-related protein 8/14 via gadolinium immunonanoparticles. Arterioscler Thromb Vasc Biol. 2012;32:962–970. 
• Maiseyeu A, Mihai G, Roy S, Kherada N, Simonetti OP, Sen CK, Sun Q, Parthasarathy S, Rajagopalan S. Detection of macrophages via paramagnetic vesicles incorporating oxidatively tailored cholesterol ester: an approach for atherosclerosis imaging. Nanomedicine. 2010;5:1341–1356. 
• Maiseyeu A, Mihai G, Kampfrath T, Simonetti OP, Sen CK, Roy S, Rajagopalan S, Parthasarathy S. Gadolinium-containing phosphatidylserine liposomes for molecular imaging of atherosclerosis. J Lipid Res. 2009;50:2157–2163.