Size is important in particle therapy for trauma

The new analysis provides guidance on the size of nanoparticles that may be most effective in stopping internal bleeding. Credits: Christine Daniloff, MIT

Traumatic injuries are the leading cause of death in the United States among people under the age of 45, and such injuries account for more than 3 million deaths annually worldwide. To reduce the death toll of such injuries, many researchers can reduce the site of internal injuries and attract cells to help stop bleeding until the patient arrives at the hospital for further treatment. We are working on injectable nanoparticles.

Some of these particles have been shown to be promising in animal studies, but none have been tested in human patients yet. One of the reasons is the lack of information on the mechanism of action and potential safety of such particles. To further shed light on these factors, MIT’s chemical engineers first looked at how polymer nanoparticles of various sizes circulate in the body and interact with platelets, the cells that promote blood clotting. I did a systematic study of.

In a rat study, researchers have shown that particles in the midsize range, about 150 nanometers in diameter, are most effective in stopping bleeding. These particles are also much less likely to migrate to the lungs and other off-target sites, and larger particles often migrate.

“Nanosystems always have some accumulation in the liver and spleen, but we want to have more active systems that accumulate in the wound than these filtration sites in the body,” says Paula, a professor at the MIT Institute. Hammond says. , Dean of the Faculty of Chemical Engineering, Member of the Koch Institute for Integrated Cancer at MIT.

Hammond; Bradley Olsen, Alexander and I. Michael Casser, Professor of Chemical Engineering. George Bermajos, Harvard Medical School Surgery Professor and Head of Trauma, Emergency Surgery, and Critical Surgical Care at Massachusetts General Hospital, is the senior author of this study.

Celestine Hong, a graduate student at MIT, is the lead author of a paper published in a journal. ACS Nano..

Size effect

Nanoparticles that can stop bleeding, also called hemostatic nanoparticles, can be made in a variety of ways. One of the most commonly used strategies is to create nanoparticles made of biocompatible polymers that are bound to proteins or peptides that attract platelets, the blood cells that initiate blood clotting.

In this study, researchers used a polymer called PEG-PLGA bound to a peptide called GRGDS to make the particles. Most of the research on polymer particles to stop bleeding has focused on particles sized from 300 to 500 nanometers. However, few studies have systematically analyzed how size affects the function of nanoparticles.

“We were actually trying to find out how the size of nanoparticles affects their interaction with wounds, which has never been investigated with polymer nanoparticles used as hemostatic agents. It’s an area, “says Hong.

Studies in animals have shown that larger nanoparticles can help stop bleeding, but those particles also tend to accumulate in the lungs, where they can cause unwanted coagulation. In a new study, the MIT team analyzed a variety of nanoparticles, including small (less than 100 nanometers), medium (140-220 nanometers), and large (500-650 nanometers).

First, they analyzed the particles in the laboratory and studied how they interact with active platelets under a variety of conditions. One of their tests measured how well the particles bind to the platelets as they flow through the tube. In this test, the smallest nanoparticles resulted in the highest percentage of bound platelets. In another test, they measured how well the nanoparticles could adhere to a platelet-coated surface. In this scenario, the largest nanoparticles adhered best.

Next, the researchers asked a slightly different question and analyzed how much of the mass attached to the surface was nanoparticles and how much was platelets. The ultimate goal is to attract as many platelets as possible. Using that benchmark, they found that intermediate particles were the most effective.

“If you attract a bundle of nanoparticles and they block platelet They bind to agglomerate with each other, which is not very convenient. I want you to put in platelets, “Hong said. “We did that experiment and found that the intermediate particle size eventually resulted in the highest platelet content.”

Stop bleeding

Next, researchers tested three size classes of nanoparticles in mice. First, they injected particles into healthy mice to study when they circulate in the body and where they accumulate. They found that the largest particles were more likely to accumulate in the lungs or other non-targeted sites, and their circulation time was shorter, as seen in previous studies.

Next, in collaboration with MGH collaborators, the researchers used a rat model of internal injury to study the most effective particles to stop bleeding. They found that medium-sized particles appeared to work best, and that they also showed the highest rate of accumulation at the wound site.

“This study is Nanoparticles It’s not necessarily the system we want to pay attention to, and I think it wasn’t clear from the previous work. Being able to focus on this medium-sized range could open up some new doors, “says Hammond.

Researchers now want to test these medium-sized particles on larger animal models for more information on their safety and the most effective doses. Ultimately, they hope that such particles can be used as the first line of treatment to stop bleeding. Traumatic injury Long enough for the patient to arrive at the hospital.

“They are particle The purpose is to deal with preventable death. Not all of these are cures for internal bleeding, but they are intended to give you a few more hours of extra time before you arrive at a hospital where you can get the right treatment, “Hong said.

Researchers are developing next-generation artificial platelets that can stop bleeding from injuries faster

For more information:
Celestine Hong et al, Understanding Nanoparticle Size Adjustments to Understand Factors Affecting Hemostasis and Maximizing Survival in Fatal Inferior Vena Cava Injury Models, ACS Nano (2022). DOI: 10.1021 / acsnano.1c09108

This story has been republished in courtesy of MIT News (, A popular site that covers news about MIT research, innovation and education.

Quote: Particles of traumatic injury (February 16, 2022) obtained from // on February 16, 2022. Size issues in processing

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Size is important in particle therapy for trauma

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