Synthetic platelets
Nanoparticles imitating the properties of human platelets have been synthesized
LifeSciencesToday based on UC Santa Barbara: Bio-Inspired Bleeding ControlRapid stopping of bleeding from a wound remains the Holy Grail of clinical medicine.
Blood flow control is a task of great importance and the first line of defense for both patients and doctors in many situations – from injuries to a number of diseases and surgery. If the bleeding cannot be stopped within the first few minutes, the further actions of the doctors actually lose their meaning.
In search of ways to control the complex process of blood coagulation, scientists at the University of California at Santa Barbara (University of California - Santa Barbara), representing the Department of Chemical Engineering and the Center for Bioengineering (Center for Bioengineering, CBE), turned to the mechanisms of thrombosis working in the human body itself. By creating nanoparticles that mimic the shape, flexibility and surface biology of the body's own platelets, they were able to accelerate the natural processes of vascular repair, and also opened the way to personalized treatment methods adapted to the needs of a particular patient.
"This is an important milestone in the development of synthetic platelets, as well as in targeted drug delivery," says Professor Samir Mitragotri, PhD, Director of CBE, specializing in targeted therapy technologies. The results of his latest work are published in the journal ACS Nano (Anselmo et al., Platelet-like Nanoparticles: Mimicking Shape, Flexibility, and Surface Biology of Platelets To Target Vascular Injuries).
The process of coagulation is well known to everyone who has received even minor injuries – scratches or cuts. Blood rushes to the site of damage to the vessel, and within a few minutes the bleeding stops as a result of the formation of a blood clot. Having fulfilled its function, the thrombus dissolves after a while.
But what we don't see is a cascade of successive stages of blood clotting – a series of biochemical signals that promote thrombosis. Coagulation, in fact, is a complex choreography of various substances and cells, among the most important of which are platelets that accumulate at the site of damage to the vessel and form the initial blood clot.
"As long as platelets are in the bloodstream, they are relatively inert," explains lead study author Aaron Anselmo, PhD. However, in case of injury – due to the physics of their shape and the response to chemical stimuli – they rush to the wall of the blood vessel and accumulate there, interacting with the site of injury and with each other. In this case, platelets release chemicals that attract other platelets to the injury site, eventually clogging the wound.
But what happens if the injury is too severe, if the patient is forced to take anticoagulants, or if for some other reason he has a reduced ability to thrombosis, which manifests itself even with a minor injury?
In these situations, nanoparticles (platelet-like nanoparticles, PLNs) that perform the function of platelets can come to the rescue. These tiny plate-shaped particles, which behave in the same way as their natural counterparts, can be injected into the blood to replenish the patient's own supply of platelets, thereby stopping bleeding and initiating the healing process. This will allow doctors to start or continue the necessary treatment. Now emergency conditions can be taken under more effective control, injuries can be healed faster and patients will be able to recover with fewer complications.
"We can really reduce the bleeding time by 65 percent...," comments Dr. Anselmo.
According to Professor Mitragotri, the key to the success achieved by him and his colleagues was to simulate the real process of thrombosis. Imitating the shape and plasticity of natural platelets, PLNs can arrive at the site of injury and accumulate there. Moreover, having a surface functionalized by the same biochemical motifs as their natural human counterparts, PLNs attract other platelets to the injury site and bind to them, increasing the likelihood of the formation of a vital blood clot. In addition, and this is very important, synthetic platelets are designed in such a way that they dissolve in the blood when the need for their presence disappears. This minimizes the complications that may occur during emergency hemostasis.
"The fact is that hemostatic drugs need to be administered in the proper amount," explains Professor Mitragotri. "Introducing both too many and too few of them will lead to problems."
According to Dr. Anselmo, with similar surface properties and shape, nanoscale particles can work even better than platelets, whose size is measured in microns. In addition, this technology makes it possible to adapt PLNs to other therapeutic agents needed by patients with a particular disease.
Platelets have an innate ability to accumulate at the vascular wall and specifically interact with the site of injury to the vessel. These platelet functions are mediated by their shape, flexibility, and complex surface interactions. American chemical engineers and bioengineers have developed nanoparticles that perform functions similar to those of natural platelets, including marginalization directed to the site of vessel damage, site-specific adhesion and enhancement of site-specific aggregation. These nanoparticles (platelet-like nanoparticles, PLNs) mimic four main characteristics of platelets: disc-shaped morphology, mechanical flexibility, biochemically and biophysically mediated aggregation and heteromultivalent presentation of ligands mediating both adhesion to Willebrand factor and collagen, and the specific formation of clusters with activated platelets. PLNs demonstrate enhanced surface binding compared to spherical and hard disk-shaped analogues, as well as site-selective adhesion and platelet aggregation properties under conditions of physiological blood flow in vitro. In vivo studies on a mouse model have shown that PLNs accumulate at the site of injury and cause a decrease in bleeding time (~65%), effectively imitating and improving the hemostatic functions of natural platelets. (Fig. ACS Nano)"This technology can solve a lot of clinical problems," says Dr. Scott Hammond, director of Translational Medicine Research Laboratories UCSB.
"Today, one of the biggest problems in clinical medicine – and it is very expensive – is that we live longer, and people are more likely to end up on blood thinners in the end. If an elderly patient comes to the clinic, this is a huge problem, because you have no idea what his medical history is, and you may need to take prompt measures."
With optimized PLNs, the targets of which are the sites of blood clots, doctors will be able to maintain a delicate balance between anticoagulant therapy and wound healing in elderly patients without causing unwanted bleeding. In other cases, antibiotic-carrying nanoparticles will be able to neutralize blood-borne pathogens and other infectious agents. For more reliable diagnostics and truly targeted therapy, nanoparticles can be designed so that they will fall into certain parts of the body – for example, into the brain, passing through the blood-brain barrier.
In addition, according to the researchers, the synthetic PLNs they have created are cheaper and have a longer shelf life than natural human platelets – a great advantage in situations of urgent need for this blood component. The ability to store them longer in these cases is essential.
In the near future, bioengineers plan to find out how the technology and synthesis of PLNs correspond to the possibility of their production on an industrial scale, as well as to address a number of practical issues related to the transfer of this technology from the laboratory to the clinic, in particular, the production, storage, sterility and stability of synthetic platelets. In addition, they are preparing for preclinical and clinical trials of their development.
Portal "Eternal youth" http://vechnayamolodost.ru17.11.2014