Sribas Chowdhury, Adamas University, Kolkata
Cardiovascular diseases are the biggest cause of death in the world right now. As of the 2019 census, over 17.9 million people died of heart attack or other heart-related ailments. And the most common cause of cardiovascular disease is atherosclerosis. Recently, scientists at the Jiao Tong University used nanoparticles as a carrier to deliver a therapeutic agent to treat atherosclerosis.
Nanotechnology in medicine
Nanotechnology involves the manipulation of matter at the atomic and subatomic levels. This mainly includes working with extremely small molecules, whose size is the range of nanometers (1mm = 1×10^-9 m). These microscopic molecules are known as nanoparticles. It is a rapidly growing field in various industries like electronics, food, and medicine.
Nanotechnology is used in medicine mainly for therapeutic purposes. This includes drug delivery, gene therapy as well as diagnosis of certain diseases. The biggest advantage of nanoparticles is that they can fasten the working of a drug or any other molecule by almost 1000 times. If a conventional tablet takes 2-3 days to be fully effective, nanoparticle-targeted therapy can do that within a day. The side effects are also minimal, thereby allowing a non-invasive and faster recovery. In this particular paper, the scientists made a nanoparticle carrier to deliver a cytokine that cures atherosclerosis.
Atherosclerosis and IL-1
Atherosclerosis is the clogging of arterial walls by deposition of certain metabolites and fat. It results in increased blood pressure and poses a danger of a heart attack. While there are many therapies to cure atherosclerosis, an anti-inflammatory targeted therapy using an inhibitory cytokine along with copper ions has the most promising prospects.
In atherosclerosis, it has been observed that macrophages play a major role. They secrete certain cytokines, which leads to an inflammatory response in the arterial walls. The cytokine, IL-1 is the major contributor to this response. So, the targeted therapy uses a cytokine that acts as an antagonist (an antagonist is a substance that inhibits the activity of another specific substance), along with copper ions. The antagonist cytokine is IL-1Ra which binds to the receptor sites and inhibits the activity of ILR1 and copper ions inhibit the activity and production of macrophages.
Nanoparticle carrier
While IL-1Ra along with Cu ion therapy is promising, it has its own sets of challenges. It carries the danger to cause liver damage and can also have limited activity due to its short half-life (4-6 h). Hence, a targeted delivery system was needed so that it could be delivered to the correct place and the problem can be cured efficiently.
The scientists used a nanoparticle-targeted therapy named Mesoporous Silver Nanoparticle (MSN). They have been quite popular in biomedical uses due to their surface area and easily adjustable volumes. For the study, the MSN particles were made using a gel-sol reaction. Then IL-1Ra was loaded into the micropores of the particle along with Cu ions. The team then checked the biocompatibility of the particles through UV ray spectroscopy, RNA sequencing, etc. The MSNs were then surgically inserted into a batch of mice with atherosclerosis. After 4 weeks, the mice were sacrificed and their carotid arteries and blood were obtained for investigation.
Observations
After obtaining the arteries, the scientists observed that the blood samples showed significantly fewer levels of cytokines like IL-1, IL-6 which are involved in an inflammatory response in atherosclerosis. After a historical analysis of the arteries, the team saw that the MSN with Il-Ra reduced lipid deposition in inner arterial walls. The macrophage count was also remarkably lesser, thereby, indicating that the therapy had also inhibited inflammatory response.
Conclusion and future prospects
The study solidified the potential of using the nanoparticle-targeted therapy, MSN as a targeted delivery system to deliver Il-1Ra as a cure for atherosclerosis. In vivo data demonstrated that the inflammation-targeted system effectively reduced arterial wall thickness, lipid deposition, and macrophage infiltration. As for future prospects, the long-term effects and biosafety of using the MSN as carriers for targeted therapy will need further investigation and research. This can potentially lead to new prospects in non-invasive and quick healing methods of patients across the world.
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Reference:
- Wu, Z., Xu, Z., Pu, H., Li, W., Liu, J., Zhao, Z., Lu, X., Lin, K., & Li, B. (2021). Degradable co-delivery nanoplatforms for inflammation-targeted therapy against atherosclerosis. Applied Materials Today, 25, 101214. https://doi.org/10.1016/j.apmt.2021.101214
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