心血管疾病新纳米疗法治疗或将问世

Researchers at MIT麻省理工学院 and Harvard Medical School have built targeted nanoparticles纳米粒子 that can cling to依靠，坚持 artery walls and slowly release medicine, an advance that potentially provides an alternative to drug-releasing stents分配的任务，支架 in some patients with cardiovascular disease心血管疾病. The particles, dubbed "nanoburrs" because they are coated with tiny protein fragments that allow them to stick to target proteins, can be designed to release their drug payload over several days. They are one of the first such particles that can precisely home in on damaged vascular tissue脉管组织，血管组织, says Omid Farokhzad, associate professor at Harvard Medical School and an author of a paper describing the nanoparticles in the Jan. 18 issue of the Proceedings of the National Academy of Sciences.

Farokhzad and MIT Institute Professor Robert Langer, also an author of the paper, have previously developed nanoparticles that seek out搜出，找出 and destroy tumors.

The nanoburrs are targeted to a specific structure, known as the basement membrane膜，薄膜, which lines the arterial walls and is only exposed when those walls are damaged. Therefore, the nanoburrs could be used to deliver drugs to treat atherosclerosis动脉硬化 and other inflammatory炎症的 cardiovascular diseases. In the current study, the team used paclitaxel紫杉醇, a drug that inhibits cell division and helps prevent the growth of scar tissue that can clog阻塞，障碍 arteries.

"This is a very exciting example of nanotechnology and cell targeting in action that I hope will have broad ramifications分枝，分叉," says Langer.

The researchers hope the particles could become a complementary approach that can be used with vascular血管的 stents, which are the standard of care for most cases of clogged and damaged arteries, or in lieu of代替 stents in areas not well suited to them, such as near a fork in the artery.

The particles, which are spheres球体 60 nanometers in diameter, consist of three layers: an inner core containing a complex of the drug and a polymer聚合物 chain called PLA; a middle layer of soybean lecithin大豆卵磷脂, a fatty material; and an outer coating of a polymer called PEG, which protects the particle as it travels through the bloodstream.

The drug can only be released when it detaches from the PLA polymer chain, which occurs gradually by a reaction called ester酯 hydrolysis水解作用. The longer the polymer chain, the longer this process takes, so the researchers can control the timing of the drug's release by altering the chain length. So far, they have achieved drug release over 12 days, in tests in cultured cells.

In tests in rats, the researchers showed that the nanoburrs can be injected intravenously通过静脉，静脉注射地 into the tail and still reach their intended target — damaged walls of the left carotid artery颈动脉. The burrs bound to the damaged walls at twice the rate of nontargeted nanoparticles.

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, says Juliana Chan, a graduate student in Langer's lab and lead author of the paper.

How they did it: The researchers screened a library of short peptide缩氨酸 sequences to find one that binds most effectively to molecules on the surface of the basement membrane. They used the most effective one, a seven-amino-acid sequence dubbed C11, to coat the outer layer of their nanoparticles.

Next steps: The team is testing the nanoburrs in rats over a two-week period to determine the most effective dose for treating damaged vascular tissue. The particles may also prove useful in delivering drugs to tumors.

"This technology could have broad applications across other important diseases, including cancer and inflammatory diseases where vascular permeability弥漫，渗透性 or vascular damage is commonly observed," says Farokhzad.