Featured Research

from universities, journals, and other organizations

Novel nanotherapeutic delivers clot-busting drugs directly to obstructed blood vessels

Date:
July 5, 2012
Source:
Wyss Institute for Biologically Inspired Engineering at Harvard
Summary:
Researchers have developed a novel biomimetic strategy that delivers life-saving nanotherapeutics directly to obstructed blood vessels, dissolving blood clots before they cause serious damage or even death. This new approach enables thrombus dissolution while using only a fraction of the drug dose normally required, thereby minimizing bleeding side effects that currently limit widespread use of clot-busting drugs.

The shear-activated nanotherapeutic breaks apart and releases its drug when it encounters regions of vascular narrowing.
Credit: Image courtesy of Wyss Institute for Biologically Inspired Engineering at Harvard

Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have developed a novel biomimetic strategy that delivers life-saving nanotherapeutics directly to obstructed blood vessels, dissolving blood clots before they cause serious damage or even death. This new approach enables thrombus dissolution while using only a fraction of the drug dose normally required, thereby minimizing bleeding side effects that currently limit widespread use of clot-busting drugs.

The research findings, which were published online July 5 in the journal Science, have significant implications for treating major causes of death, such as heart attack, stroke and pulmonary embolism, that are caused by acute vascular blockage by blood thrombi.

The inspiration for the targeted vascular nanotherapeutic approach came from the way in which normal blood platelets rapidly adhere to the lining of narrowed vessels, contributing to the development of atherosclerotic plaques. When vessels narrow, high shear stresses provide a physical cue for circulating platelets to stick to the vessel wall selectively in these regions. The vascular nanotherapeutic is similarly about the size of a platelet, but it is an aggregate of biodegradable nanoparticles that have been coated with the clot-busting drug, tissue plasminogen activator (tPA). Much like when a wet ball of sand breaks up into individual grains when it is sheared between two hands, the aggregates selectively dissociate and release tPA-coated nanoparticles that bind to clots and degrade them when they sense high shear stress in regions of vascular narrowing, such as caused by blood clot formation.

Disruption of normal blood flow to the heart, lung, and brain due to thrombosis is one of the leading causes of death and long-term adult disability in the developing world. Today, patients with pulmonary embolism, strokes, heart attacks and other types of acute thrombosis leading to near-complete vascular occlusion, are most frequently treated in an acute care hospital setting using systemic dosages of powerful clot-dissolving drugs. Because these drugs can cause severe and often fatal bleeding as they circulate freely throughout the body, the size of the dosage given to any patient is limited because efficacy must be balanced against risk.

The new shear-activated nanotherapeutic has the potential to overcome these efficacy limitations. By targeting and concentrating drug at the precise site of the blood vessel obstruction, the Wyss team has been able to achieve improved survival in mice with occluded lung vessels with less than 1/50th of the normal therapeutic dose, which should translate into fewer side effects and greater safety. This raises the possibility that, in the future, an emergency technician might be able immediately administer this nanotherapeutic to anyone suspected of having a life-threatening blood clot in a vital organ before the patient even reached the hospital.

The inter-disciplinary and inter-institutional collaborative research team, which was led by Wyss Founding Director Donald Ingber M.D., Ph.D. and Wyss Technology Development Fellow Netanel Korin, Ph.D., also included Wyss postdoctoral Fellow Mathumai Kanapathipillai, Ph.D. as well as Benjamin D. Matthews, Marilena Crescente, Alexander Brill, Tadanori Mammoto, Kaustabh Ghosh, Samuel Jurek, Sidi A. Bencherif, Deen Bhatta, Ahmet U. Coskun, Charles L. Feldman, and Denisa D. Wagner from Brigham and Women's Hospital, Children's Hospital Boston, Harvard Medical School, the Harvard School of Engineering and Applied Sciences, and Northeastern University. Ingber is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Children's Hospital Boston, and Professor of Bioengineering at Harvard's School of Engineering and Applied Sciences.

Commenting on the work, Ingber noted that "the vascular nanotherapeutic we developed that selectively becomes activated in regions of high shear stress, much like living platelets do, is a wonderful example of how we at the Wyss Institute take inspiration from biology, and how biomimetic strategies can lead to new and unexpected solutions to age-old problems that existing technologies can't address."


Story Source:

The above story is based on materials provided by Wyss Institute for Biologically Inspired Engineering at Harvard. Note: Materials may be edited for content and length.


Journal Reference:

  1. Netanel Korin, Mathumai Kanapathipillai, Benjamin D. Matthews, Marilena Crescente, Alexander Brill, Tadanori Mammoto, Kaustabh Ghosh, Samuel Jurek, Sidi A. Bencherif, Deen Bhatta, Ahmet U. Coskun, Charles L. Feldman, Denisa D. Wagner, Donald E. Ingber. Shear-Activated Nanotherapeutics for Drug Targeting to Obstructed Blood Vessels. Science, July 5 2012 DOI: 10.1126/science.1217815

Cite This Page:

Wyss Institute for Biologically Inspired Engineering at Harvard. "Novel nanotherapeutic delivers clot-busting drugs directly to obstructed blood vessels." ScienceDaily. ScienceDaily, 5 July 2012. <www.sciencedaily.com/releases/2012/07/120705181246.htm>.
Wyss Institute for Biologically Inspired Engineering at Harvard. (2012, July 5). Novel nanotherapeutic delivers clot-busting drugs directly to obstructed blood vessels. ScienceDaily. Retrieved April 20, 2014 from www.sciencedaily.com/releases/2012/07/120705181246.htm
Wyss Institute for Biologically Inspired Engineering at Harvard. "Novel nanotherapeutic delivers clot-busting drugs directly to obstructed blood vessels." ScienceDaily. www.sciencedaily.com/releases/2012/07/120705181246.htm (accessed April 20, 2014).

Share This



More Health & Medicine News

Sunday, April 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Nine-Month-Old Baby Can't Open His Mouth

Nine-Month-Old Baby Can't Open His Mouth

Newsy (Apr. 19, 2014) Nine-month-old Wyatt Scott was born with a rare disorder called congenital trismus, which prevents him from opening his mouth. Video provided by Newsy
Powered by NewsLook.com
'Holy Grail' Of Weight Loss? New Find Could Be It

'Holy Grail' Of Weight Loss? New Find Could Be It

Newsy (Apr. 18, 2014) In a potential breakthrough for future obesity treatments, scientists have used MRI scans to pinpoint brown fat in a living adult for the first time. Video provided by Newsy
Powered by NewsLook.com
Little Progress Made In Fighting Food Poisoning, CDC Says

Little Progress Made In Fighting Food Poisoning, CDC Says

Newsy (Apr. 18, 2014) A new report shows rates of two foodborne infections increased in the U.S. in recent years, while salmonella actually dropped 9 percent. Video provided by Newsy
Powered by NewsLook.com
Scientists Create Stem Cells From Adult Skin Cells

Scientists Create Stem Cells From Adult Skin Cells

Newsy (Apr. 17, 2014) The breakthrough could mean a cure for some serious diseases and even the possibility of human cloning, but it's all still a way off. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins