“Nanoburrs" are nanoparticles coated with a sticky protein that makes them cling onto artery walls while they slowly release drugs that inhibit cell division and helps prevent growth of scar tissue that can clog arteries. The researchers, based at MIT and Harvard Medical School have developed and tested the nanoburrs as potential drug-releasing agents for targeting and repairing damaged blood vessels. The nanoburrs can release their drug payload over several days, and could be used to deliver drugs to treat atherosclerosis and other inflammatory cardiovascular diseases. The researchers designed the nanoburrs to target a specific structure in the artery wall, the basement membrane, which only becomes exposed when the walls are damaged. In the study they used a drug called paclitaxel that inhibits cell division and helps prevent the growth of scar tissue that can clog arteries. The nanoburrs are 60 nanometer-diameter spheres and comprise three layers: an inner core, a middle layer and an outer coating. The inner core contains the drug payload and a polymer chain called PLA. The middle layer is made of a fatty material, soybean lecithin, and the outer coating is a polymer, PEG which protects the nanoburr as it travels through the bloodstream. The drug release is controlled by varying the length of the PLA chain in the core: the longer the chain, the longer the duration of the release, which occurs through a reaction called ester hydrolysis whereby the drug becomes detached from the polymer. To make the "burrs", the researchers screened a library of short peptide sequences to find one that bound most effectively to molecules on the surface of the arterial basement membrane. They selected the most effective one, the seven-amino-acid sequenced C11, to coat the outer layer of the nanospheres. The researchers said they have managed to achieve drug release periods lasting 12 days in cultured cells. They also injected the nanoburrs intravenously into the tails of rats and showed they reached their intended target: the damaged walls of the left carotid artery (the vessel that supplies the head and neck with oxygenated blood). They found that the nanoburrs bound to the damaged walls at twice the rate of non-targeting particles. Because the particles can deliver drugs over a longer period of time, and can be injected intravenously, patients would not have to endure repeated and surgically invasive injections directly into the area that requires treatment. Nanoburrs can be used with vascular stents, the standard of care for most cases of clogged and damaged arteries, and in some cases may even replace stents in locations they are not well suited for, such as near a fork in the artery. The team is now testing the nanoburrs in rats to find the most effective dose for repairing damaged vascular tissue. This technology could have broad applications across other important diseases, including cancer and inflammatory diseases where vascular permeability or vascular damage is commonly observed.