- Post Doctoral
MIT Unit Affiliation:
- Biological Engineering
Post Doc Sponsor / Advisor:
Date PhD Completed:
Top 3 Areas of Expertise:
Expected End Date of Post Doctoral Position:
- In Vivo Utilization of Near Infrared Fluorescent Single
- Walled Carbon Nanotubes as Tissue Localizable Biosensors
A major cause of cardiovascular disease is atherosclerosis, the progressive accumulation and modification of low density lipoproteins (LDL) within the vascular wall associated with a non-reversible inflammatory cascade. Current treatments attempt to inhibit systemic LDL levels, and thus can only secondarily de-escalate the progression of atherosclerosis. This thesis investigates the mechanisms of an alternative approach based on the use of amphiphilic polymers to directly inhibit highly oxidized LDL (hoxLDL) internalization by macrophage cells, thereby retarding foam cell formation and inflammatory cytokine secretion. First the architecture of the polymers is systematically investigated to elucidate the important design facets for hoxLDL uptake inhibition by THP-1 human macrophage cells in serum and serum free media. The optimal polymer structure is found to be comprised of one, rotationally restricted carboxylic acid conjugated to the hydrophobic end of each polymer chain. Through the administration of carboxy-terminated amphiphilic polymers (AMs) the total concentration of hoxLDL within macrophage cells is lowered by 73% and when an encapsulated Liver-X Receptor (LXR) ligand is also delivered the hoxLDL accumulation is further lowered, decreased by 88%. The delivery of the AMs and drug encapsulated AMs in vivo shows a significant inhibition in cholesterol accumulation and macrophage recruitment in an injured carotid artery rat model. The AMs also inhibit inflammatory responses in vitro, significantly decreasing matrix metalloproteinase (57%) and cytokine secretion (TNFα 47% and IL-1β 59%) compared to non-treated cells. Through the inhibition of hoxLDL internalization and inflammation progression these AMs show the potential to be a new and multi-faceted cardiovascular treatment modality.
Top 5 Awards and honors (name of award, date received):
5 Recent Papers:
Iverson NM, Barone PW, Shandell M, Trudell LJ, Sen S, Sen F, Ivanov V, Atolia E, Farias E, McNicholas TP, Reuel N, Parry NMA, Wogan GN, Strano MS, In vivo biosensing via tissue localizable near-infrared fluorescent single walled carbon nanotubes. Nature Nanotechnology 2013 8(11):873-880.
Landry MP, Kruss S, Nelson JT, Bisker G, Iverson NM, Reuel NF, Strano MS, Experimental Tools to Study Molecular Recognition within the Nanoparticle Corona. Sensors 2014 14(9):16196-16211.
Ulissi ZW, Sen F, Gong X, Sen S, Iverson NM, Boghossian A, Godoy L, Wogan GN, Mukhopadhyay, Strano MS, Spatiotemporal Intracellular Nitric Oxide Signaling Captured using Internalized, Near Infrared Fluorescent Carbon Nanotube Nanosensors. Nano Letters. 2014 14(8):4887-4894.
Biskar G, Iverson NM, Ahn J, Strano MS, A Pharmacokinetic Model of a Tissue Implantable Insulin Sensor. Advanced Healthcare Materials. Advanced Healthcare Materials. 2014.
Giraldo JP, Landry MP, Faltermeier S, McNicholas TP, Iverson NM, Boghossian AA, Reuel NF, Hilmer AJ, Sen F, Brew J Strano MS, Plant nanobionics approach to augment photosynthesis and biochemical sensing. Nature Materials 2014 13(4):400-408.