By Dr Juliana Chan
Towards my PhD thesis in the lab of Bob Langer at the Massachusetts Institute of Technology (MIT), I engineered targeted hybrid polymeric-lipid nanoparticles that can cling to artery walls and slowly release medicine. Targeted nanotechnologies that can precisely home in on damaged vascular tissue are a newer application in the field of drug delivery, as most studies have focused on targeting tumors.
The particles I designed are 60 nanometers in diameter and consist of three layers: an inner core containing an anti-proliferative drug, paclitaxel; a middle layer of soybean lecithin, a fatty material; and an outer coating of a polymer called PEG, which protects the particle as it travels through the bloodstream. I screened a library of short peptide sequences to find one that binds most effectively to molecules on the surface of the basement membrane, and I chose the most effective seven amino-acid sequence to coat the outer layer of their nanoparticles.
I named this nanoparticle technology "nanoburrs", because the nanoparticles are coated with tiny protein fragments that allow them to stick to target proteins, similar to how burrs (seeds) stick to our clothing without letting go. I designed the particles in hope that they could become a complementary approach that can be used with vascular stents, the standard of care for stenotic arteries, or in lieu of stents in areas not well suited to them, such as near a fork in the artery (bifurcation).
In 2011, we published a follow up paper, also in PNAS, which showed that the nanoburrs delivered by intravenous injection could reduce the level of arterial stenosis by 50% in a rat balloon injury model over a two-week period.