Feb 22 2022

Using Nanoparticles to Stop Internal Bleeding

“Nanotechnology” is one of the buzzwords of our time. It is used the exact same way “space age technology” was used in the last few decades of the 20th century, and to a lesser extent even to today. It creates a marketing halo of advanced cutting-edge technology, but it’s not clear what it actually means. The term has loosely been used to refer to any tech that involves any component that has one dimension which is between 1-100 nanometers (nm). If only one dimension is in this size range then we are dealing with a nanosheet, and if one of the remaining two dimensions is a lot longer than the other this is a nanoribbon. If two dimensions are in the nano range then that is a nanofiber (long) or nanorod (short), and if it’s hollow then a nanotube. If all three dimensions are between 1-100 nm then that is a nanoparticle.  The nanoparticles themselves could be anything. Since many natural substances have features in this size range, it’s easy to invoke the “nanotechnology” buzzword. For this reason synthetic machines that operate on the nanoscale have been dubbed “molecular nanotechnology” to distinguish this from the now overused regular nanotechnology label.

That said, the ability to determine and control features of objects at the nanoscale is incredibly useful, and in many areas of material science is taking our technology to the next level. We are not yet at the point where we can create sophisticated nanomachines to do our bidding at the nanoscale, but that is the long-term goal. In the meantime we are finding lots of uses for nanoparticles, specifically in medicine. It has been argued that biology is nanotechnology, and if we want to interact with biological systems at their most fundamental scale then we need to get down to the nanoscale. One potential application of nanoparticle medicine is to reduce internal bleeding.

Trauma is the number one cause of death in people 45 years of age and younger. Internal bleeding is a major contributor to trauma-related death, because it may be difficult to identify prior to getting to a hospital, and it may be difficult or even impossible to stop the bleeding by applying pressure. In fact there are technical terms for such bleeds, such as noncompressible torso hemorrhage (NCTH). But what if we can help stop the bleeding from the inside?

The body, of course, contains its own nanotechnology to stop bleeding. The first line of defense is platelets, which are sticky cell fragments that circulate in the blood. They will stick to sites of injury and stick to each other, forming a rapid internal patch to stop any bleeding while longer term mechanisms (fibrous tissue) have a chance to more thoroughly stop the bleeding until wound healing can take place. Research is under way to develop nanoparticles that can essentially help the platelets do their job more quickly and thoroughly, for serious life-threatening internal bleeds, giving patients time to get to the operating room. There are two basic types of hemostatic nanoparticles, as they are called – biological and synthetic. Biological nanoparticles are derived from living cells or organelles. They have a major disadvantage, however, in that they can provoke an immune response. This is not necessarily an unsolvable problem, but is a barrier for now.

So research has focused on synthetic hemostatic nanoparticles, that can be engineered to not provoke a significant immune response. These are still made from biological material, however. The main candidates are liposomes, little bubbles of fat, which are engineered to have specific peptides (protein fragments) or other modifications on their surface.  So far this technology is in the animal research phase and has not yet progressed to human trials. Researchers are still trying to work out some of the basics, such as the optimal size of hemostatic nanoparticles to do the job. That is the focus of a recent study, both in-vitro and in-vivo. They examined the effects of nanoparticles ranging from <100 nm to 500 nm, so stretching the definition of nanoparticle a bit.

These are passive nanoparticles, not machines that can direct their own activity. They are simply injected into a vein or artery and then go with the flow. The main question is – where do they go and what do they do? Ideally we want the hemostatic nanoparticles to primarily accumulate at the site of injury. We also want them to stick to the site of the bleed and stick to platelets, helping the platelets to more quickly bunch up and stop the bleeding. We don’t want them to stick to each other too much, however, because we don’t want them to replace platelets at the injury site, we want them to increase platelet aggregation there. Researchers are looking, therefore, for a complex of mostly platelets and some nanoparticles. We also do not want the particles to get filtered out quickly by the spleen or liver, and we don’t want them to accumulate in the lungs and form clots there.

Larger nanoparticle size tended to get filtered in the organs and did not accumulate as much at the site of injury. The filtering also means they had a lower lifetime in the blood. Small and medium sized particles were filtered less and survived longer. The smallest nanoparticles, however, did not significantly slow bleeding. Therefore the intermediate particles, in the 150 nm range, were in the Goldilocks zone – they survived the longest, had the greatest accumulation a the site of injury, and slowed the bleeding the most. In a rat model where the vena cava was injured, two hour survival time was increased with the intermediate nanoparticles.

This information is critical to moving forward with this research, but we are not ready for human trials yet. It’s great to know the ideal size for hemostatic nanoparticles, but this can be dialed in further, and also we can study mixed particle sizes further. Also, there are the details of the nanoparticles themselves – which activating components to include in the lisosomes. Human trials will take time, of course, but it is likely that in 5-10 years (I know – this time frame is a cliche of technological development, but it is a reasonable time frame) it may become standard for emergency responders and trauma centers to routinely inject trauma victims with hemostatic nanoparticles to reduce internal bleeding.


No responses yet