Heart nanotechnology

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Heart nanotechnology is the "Engineering of functional systems at the molecular scale" ("Nanotechnology Research"). [1]

Contents

Nanotechnology

Nanotechnology deals with structures and materials that are approximately one to one-hundred nanometers in length. At this microscopic level, quantum mechanics take place and are in effect, resulting in behaviors that would seem quite strange compared to what humans see with the naked eye (regular matter). Nanotechnology is used for a wide variety of fields of technology, ranging from energy to electronics to medicine. In the category of medicine, nanotechnology is still relatively new and has not yet been widely adopted by the field. It is possible that nanotechnology could be the new breakthrough of medicine and may eventually be the solution and cure for many of the health problems that humans encounter. Nanotechnology may lead to the cure for illnesses such as the common cold, diseases, and cancer. It is already starting to be used as a treatment for some serious health issues; more specifically it is being used to treat the heart and cancer.[ citation needed ]

Nanomedicine

Nanotechnology in the field of medicine is more commonly referred to as nanomedicine. Nanomedicine that deals with helping the heart is really starting to take off and gain in popularity compared to most of the other fields that nanomedicine currently has to offer. There are several heart problems that nanotechnology has promising evidence of being effective in the treatment of heart disease in the near future.

Examples

It should hopefully be able to treat heart valves that are defective; and detect and treat arterial plaque in the heart ("Nanotechnology Made Clear"). Nanomedicine should be able to help heal the hearts of people that have already been victims of heart disease and heart attacks. On the other hand, it will also play a key role in finding people with a high risk of having heart disease, and will be able to help prevent heart attacks from happening in the first place. Nanotechnology of the heart is a lot less invasive than surgery because everything is occurring at a minuscule level in the body compared to relatively large tissues that are dealt with in surgery. With our technology today, heart surgeries are performed to treat the damaged heart tissue that resulted from a heart attack. This is a major surgery that usually takes a couple of months to recover from ("WebMD - Better Information. Better Health"). During this period, patients are extremely limited in the activities that they can do. This long recovery process is an inconvenience to the patients, and with the growth of medicine it most likely won't be very long before a more efficient method for treating heart attack patients will be developed and used.[ citation needed ] The method that is the frontrunner to replace major heart surgery is the use of nanotechnology. There are a couple alternate ways to heart surgery that nanotechnology will potentially be able to offer in the future.

Alternatives to surgery

With people that have heart disease or that have suffered a heart attack, their hearts are often damaged and weakened. The more minor forms of heart failure do not require surgery and are often treated with medications ("WebMD - Better Information. Better Health"). The use of nanotechnology on treating damaged hearts will not replace these milder heart problems, but rather the more serious heart problems that currently require surgery or sometimes even heart transplants.

Heart repair

A group of engineers, doctors and materials scientists at MIT and Children's Hospital Boston have teamed together and are starting the movement of finding a way to use nanotechnology to strengthen the weakened heart tissue ("MIT - Massachusetts Institute of Technology"). The first method uses nanotechnology combined with tissue engineering, and gold nanowires are placed and woven into the damaged parts of the heart, essentially replacing the non-functioning or dead tissues. [2]

Tissue regeneration

The other approach would potentially use minuscule nanoparticles that would travel through the body and find dying heart tissue. The nanoparticles would be carrying objects such as "stem cells, growth factors, drugs and other therapeutic compounds,". [2] Then the nanoparticles would release the compounds and inject them into the damaged heart tissue. This would theoretically lead to the regeneration of the tissue. [2]

Heart repair difficulties

Being able to fix cardiac tissue that has been damaged from a heart attack or heart disease is not very simple and it is one of the major challenges today in the field of tissue engineering ("Popular Science"). This is because heart cells are not the easiest objects to create in a lab. It takes an enormous amount of special care and work to develop the cells so that they beat in sync with one another ("Popular Science"). Even after the heart cells have finally been made, it is also a large task to insert the cells into the inoperable parts of the heart and to get them working in unison with the tissues that were still working properly ("Popular Science").

Heart patches

There have been several successful examples of this with the use of a "stem-cell- based heart patch developed by Duke University researchers," ("Popular Science"). The biomaterials that make up the patch are usually made of either biological polymers like alginate or synthetic polymers such as polylactic acid ("Nature Nanotechnology"). These materials are good at organizing the cells into functioning tissues; however they act as insulators and are poor conductors of electricity, which is a major problem especially in the heart ("Nature Nanotechnology"). Since the electrical signals that are sent between calcium ions are what control when the cardiomyocytes of the heart contract, which makes the heart beat, the stem-cell heart patch is not very efficient and not as effective as doctors would like it to be ("Popular Science"). The results of the patch not being very conductive is that the cells are not able to attain a smooth, continuous beat throughout the entire tissue containing the stem cells. This results in the heart not functioning properly, which in turn could mean that more heart problems might arise due to the implanting of the stem cells.

Tissue scaffolds

Recently[ when? ] there have been some new developments in the field of nanotechnology that will be more efficient than the poorly conducting stem-cell-based patch ("Nature Nanotechnology"). Scientists and researchers found a way for these stem cell patches (also known as tissue scaffolds) to be conductive and therefore become exponentially[ citation needed ] more effective ("Nature Nanotechnology"). They found that by growing gold nanowires into and through the patches, they were able to greatly increase the electrical conductivity. [2] The nanowires are thicker than the original scaffold and the cells are better organized as well. [2] There is also an increase in production of the proteins needed for muscle calcium binding and contraction. [2] The gold nanowires poke through the stem cell's scaffolding material, which strengthens the electrical communication between surrounding heart cells. [2] Without the nanowires, the stem cell patches produced a minute current and the cells would only beat in small clusters at the stimulation origin. [2] With the nanowires, the cells seem to contract together even when they are clustered far away from the source of stimulation. [2] The use of gold nanowires with the stem cell heart patches is still a relatively new concept and it will probably be awhile before they will be used in humans. It is hoped that the nanowires will be tested in live animals in the near future. [2]

Nanoparticles

Another way that nanotechnology will potentially be used to help fix damaged heart tissues is through the use of guided nanoparticle "missiles". [2] These nanoparticles can cling to and attach to artery walls and secrete medicine at a slow rate ("MIT-Massachusetts Institute of Technology"). The particles, known as nanoburrs due to the fact that they are coated with little protein fragments that stick to and target certain proteins. The nanoburrs can be made to release the drug that is attached to them over the course of several days ("MIT-Massachusetts Institute of Technology"). They are unique compared to regular drugs because they can find the particular damaged tissue, attach to it, and release the drug payload that is attached to it ("MIT-Massachusetts Institute of Technology"). What happens is the nanoburrs are targeted to a certain structure, known as the basement membrane; this membrane lines the arterial walls and is only present if the area is damaged. Nanoburrs could be able to carry drugs that are effective in treating the heart, and also potentially carry stem cells to help regenerate the damaged heart tissue ("MIT-Massachusetts Institute of Technology").

Composition

The particles are made up of three different layers and are sixty nanometers in diameter ("MIT-Massachusetts Institute of Technology").The outer layer is a coating of polymer called PEG, and its job is to protect the drug from disintegrating while it is traveling through the body. The middle layer consists of a fatty substance and the inner core contains the actual drug along with a polymer chain, which controls the amount of time it will take before the drug is released ("MIT-Massachusetts Institute of Technology").

Research

In a study done on rats, the nanoparticles were injected directly into the rat's tail and they still were able to reach the desired target (the left carotid artery) at a rate that was twice the amount of the non-targeted nanoparticles ("MIT-Massachusetts Institute of Technology"). Because the particles can deliver drugs over a long period of time, and can be injected intravenously, the patients would not need to have multiple repeated injections, or invasive surgeries on the heart which would be a lot more convenient. The only downside to this is that the existing delivery approaches are invasive, requiring either a direct injection into the heart, catheter procedures, or surgical implants. [2] There is no question, however, that the future of heart repairs and heart disease/attack prevention will definitely involve the use of nanotechnology in some way.[ citation needed ]

Polyketal nanoparticles

Composition

Polyketal nanoparticles are pH-sensitive, hydrophobic nanoparticles formulated from poly(1-4-phenyleneacetone dimethylene ketal). [3] They are an acid-sensitive vehicle of drug delivery, specifically designed for targeting the environments of tumors, phagosomes, and inflammatory tissue. [3] In such acidic environments, these nanoparticles undergo accelerated hydrolysis into low molecular weight hydrophilic compounds, consequently releasing their therapeutic contents at a faster rate. [3] Unlike polyester-based nanoparticles, polyketal nanoparticles do not generate acidic degradation products following hydrolysis [3] [4]

Use in myocardial infarction

Post-myocardial infarction, inflammatory leukocytes invade the myocardium. Leukocytes contain high amounts of Nicotinamide adenine dinucleotide phosphate (NADPH) and Nox2. [5] [6] Nox2 and NADPH oxidase combine to act as a major source of cardiac superoxide production, which in excess can lead to myocyte hypertrophy, apoptosis, fibrosis, and increased matrix metalloproteinase-2 expression. [5] In a mouse-model study by Somasuntharam et al. 2013, polyketal nanoparticles were used as a delivery vehicle for siRNA to target and inhibit Nox2 in the infarcted heart. [7] Following intramyocardial injection in vivo, Nox2-siRNA nanoparticles prevented upregulation of Nox2-NADPH oxidase, and improved fractional shortening. [7] When taken up by macrophages in the myocardium following a MI, the nanoparticles degraded in the acidic environment of the endosomes/phagosomes, releasing Nox2-specific siRNA into the cytoplasm. [7]

Polyketal nanoparticles have also been used in the infarcted mouse heart to prevent ischemia-reperfusion injury caused by reactive oxygen species (ROS). [8] Levels of the antioxidant Cu/Zn-superoxide dismutase (SOD1), which scavenges harmful ROS, decrease following MI. [9] SOD1-enacapsulated polyketal nanoparticles are able to scavenge reperfusion-injury induced ROS. [8] Furthermore, this treatment improved fractional shortening, suggesting the benefit of targeted delivery by polyketals. One of the key advantages of polyketal use is that they do not exacerbate the inflammatory response, even when administered at concentrations exceeding therapeutic limits. [10] In contrast to commonly used poly(lactic-co-glycolic acid) (PLGA) nanoparticles, polyketal nanoparticle administration in mice instigates little recruitment of inflammatory cells. [10] Additionally, intramuscular injection of polyketals into the leg of rats shows no significant increases in inflammatory cytokines such as IL-6, IL-1ß, TNF-α and IL-12. [10]

Related Research Articles

Nanomedicine is the medical application of nanotechnology. Nanomedicine ranges from the medical applications of nanomaterials and biological devices, to nanoelectronic biosensors, and even possible future applications of molecular nanotechnology such as biological machines. Current problems for nanomedicine involve understanding the issues related to toxicity and environmental impact of nanoscale materials.

<span class="mw-page-title-main">Endocardium</span> Innermost layer of tissue lining the chambers of the heart

The endocardium is the innermost layer of tissue that lines the chambers of the heart. Its cells are embryologically and biologically similar to the endothelial cells that line blood vessels. The endocardium also provides protection to the valves and heart chambers.

Stephen E. Epstein is the Head of Translational and Vascular Biology Research at the MedStar Heart and Vascular Institute, MedStar Washington Hospital Center and Clinical Professor of Medicine at the Georgetown University School of Medicine.

Stem-cell therapy is the use of stem cells to treat or prevent a disease or condition. As of 2016, the only established therapy using stem cells is hematopoietic stem cell transplantation. This usually takes the form of a bone-marrow transplantation, but the cells can also be derived from umbilical cord blood. Research is underway to develop various sources for stem cells as well as to apply stem-cell treatments for neurodegenerative diseases and conditions such as diabetes and heart disease.

Targeted drug delivery, sometimes called smart drug delivery, is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. This means of delivery is largely founded on nanomedicine, which plans to employ nanoparticle-mediated drug delivery in order to combat the downfalls of conventional drug delivery. These nanoparticles would be loaded with drugs and targeted to specific parts of the body where there is solely diseased tissue, thereby avoiding interaction with healthy tissue. The goal of a targeted drug delivery system is to prolong, localize, target and have a protected drug interaction with the diseased tissue. The conventional drug delivery system is the absorption of the drug across a biological membrane, whereas the targeted release system releases the drug in a dosage form. The advantages to the targeted release system is the reduction in the frequency of the dosages taken by the patient, having a more uniform effect of the drug, reduction of drug side-effects, and reduced fluctuation in circulating drug levels. The disadvantage of the system is high cost, which makes productivity more difficult, and the reduced ability to adjust the dosages.

Cardiomyoplasty is a surgical procedure in which healthy muscle from another part of the body is wrapped around the heart to provide support for the failing heart. Most often the latissimus dorsi muscle is used for this purpose. A special pacemaker is implanted to make the skeletal muscle contract. If cardiomyoplasty is successful and increased cardiac output is achieved, it usually acts as a bridging therapy, giving time for damaged myocardium to be treated in other ways, such as remodeling by cellular therapies.

<span class="mw-page-title-main">Coronary stent</span> Medical stent implanted into coronary arteries

A coronary stent is a tube-shaped device placed in the coronary arteries that supply blood to the heart, to keep the arteries open in patients suffering from coronary heart disease. The vast majority of stents used in modern interventional cardiology are drug-eluting stents (DES) It is used in a medical procedure called percutaneous coronary intervention (PCI). Coronary stents are divided into two broad types - drug-eluting and bare metal stents, as of 2023 drug-eluting stents were used in more than 90% of all PCI procedures. Stents reduce angina and have been shown to improve survival and decrease adverse events after a patient has suffered a heart attack - medically termed an acute myocardial infarction.

<span class="mw-page-title-main">Biointerface</span>

A biointerface is the region of contact between a biomolecule, cell, biological tissue or living organism or organic material considered living with another biomaterial or inorganic/organic material. The motivation for biointerface science stems from the urgent need to increase the understanding of interactions between biomolecules and surfaces. The behavior of complex macromolecular systems at materials interfaces are important in the fields of biology, biotechnology, diagnostics, and medicine. Biointerface science is a multidisciplinary field in which biochemists who synthesize novel classes of biomolecules cooperate with scientists who have developed the tools to position biomolecules with molecular precision, scientists who have developed new spectroscopic techniques to interrogate these molecules at the solid-liquid interface, and people who integrate these into functional devices. Well-designed biointerfaces would facilitate desirable interactions by providing optimized surfaces where biological matter can interact with other inorganic or organic materials, such as by promoting cell and tissue adhesion onto a surface.

<span class="mw-page-title-main">Myocardial infarction</span> Interruption of blood supply to a part of the heart

A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction to the heart muscle. The most common symptom is chest pain or discomfort which may travel into the shoulder, arm, back, neck or jaw. Often such pain occurs in the center or left side of the chest and lasts for more than a few minutes. The discomfort may occasionally feel like heartburn. Other symptoms may include shortness of breath, nausea, feeling faint, a cold sweat, feeling tired, and decreased level of consciousness. About 30% of people have atypical symptoms. Women more often present without chest pain and instead have neck pain, arm pain or feel tired. Among those over 75 years old, about 5% have had an MI with little or no history of symptoms. An MI may cause heart failure, an irregular heartbeat, cardiogenic shock or cardiac arrest.

Nano-scaffolding or nanoscaffolding is a medical process used to regrow tissue and bone, including limbs and organs. The nano-scaffold is a three-dimensional structure composed of polymer fibers very small that are scaled from a Nanometer scale. Developed by the American military, the medical technology uses a microscopic apparatus made of fine polymer fibers called a scaffold. Damaged cells grip to the scaffold and begin to rebuild missing bone and tissue through tiny holes in the scaffold. As tissue grows, the scaffold is absorbed into the body and disappears completely.

Amniotic stem cells are the mixture of stem cells that can be obtained from the amniotic fluid as well as the amniotic membrane. They can develop into various tissue types including skin, cartilage, cardiac tissue, nerves, muscle, and bone. The cells also have potential medical applications, especially in organ regeneration.

<span class="mw-page-title-main">Myocardial scarring</span>

Myocardial scarring is the accumulation of fibrous tissue resulting after some form of trauma to the cardiac tissue. Fibrosis is the formation of excess tissue in replacement of necrotic or extensively damaged tissue. Fibrosis in the heart is often hard to detect because fibromas, scar tissue or small tumors formed in one cell line, are often formed. Because they are so small, they can be hard to detect by methods such as magnetic resonance imaging. A cell line is a path of fibrosis that follow only a line of cells.

<span class="mw-page-title-main">Arginylglycylaspartic acid</span> Chemical compound

Arginylglycylaspartic acid (RGD) is the most common peptide motif responsible for cell adhesion to the extracellular matrix (ECM), found in species ranging from Drosophila to humans. Cell adhesion proteins called integrins recognize and bind to this sequence, which is found within many matrix proteins, including fibronectin, fibrinogen, vitronectin, osteopontin, and several other adhesive extracellular matrix proteins. The discovery of RGD and elucidation of how RGD binds to integrins has led to the development of a number of drugs and diagnostics, while the peptide itself is used ubiquitously in bioengineering. Depending on the application and the integrin targeted, RGD can be chemically modified or replaced by a similar peptide which promotes cell adhesion.

Myocardial infarction complications may occur immediately following a heart attack, or may need time to develop. After an infarction, an obvious complication is a second infarction, which may occur in the domain of another atherosclerotic coronary artery, or in the same zone if there are any live cells left in the infarct.

Human HGF plasmid DNA therapy of cardiomyocytes is being examined as a potential treatment for coronary artery disease, as well as treatment for the damage that occurs to the heart after MI. After MI, the myocardium suffers from reperfusion injury which leads to death of cardiomyocytes and detrimental remodelling of the heart, consequently reducing proper cardiac function. Transfection of cardiac myocytes with human HGF reduces ischemic reperfusion injury after MI. The benefits of HGF therapy include preventing improper remodelling of the heart and ameliorating heart dysfunction post-MI.

Human engineered cardiac tissues (hECTs) are derived by experimental manipulation of pluripotent stem cells, such as human embryonic stem cells (hESCs) and, more recently, human induced pluripotent stem cells (hiPSCs) to differentiate into human cardiomyocytes. Interest in these bioengineered cardiac tissues has risen due to their potential use in cardiovascular research and clinical therapies. These tissues provide a unique in vitro model to study cardiac physiology with a species-specific advantage over cultured animal cells in experimental studies. hECTs also have therapeutic potential for in vivo regeneration of heart muscle. hECTs provide a valuable resource to reproduce the normal development of human heart tissue, understand the development of human cardiovascular disease (CVD), and may lead to engineered tissue-based therapies for CVD patients.

<span class="mw-page-title-main">Joyce Wong</span> American engineer and professor

Joyce Y. Wong is an American engineer who is Professor of Biomedical Engineering and Materials Science and Engineering at Boston University. Her research develops novel biomaterials for the early detection treatment of disease. Wong is the Inaugural Director of the Provost's Initiative to promote gender equality and inclusion in STEM at all levels: Advance, Recruit, Retain and Organize Women in STEM. She is a Fellow of the American Association for the Advancement of Science, American Institute for Medical and Biological Engineering and Biomedical Engineering Society.

Tissue engineered heart valves (TEHV) offer a new and advancing proposed treatment of creating a living heart valve for people who are in need of either a full or partial heart valve replacement. Currently, there are over a quarter of a million prosthetic heart valves implanted annually, and the number of patients requiring replacement surgeries is only suspected to rise and even triple over the next fifty years. While current treatments offered such as mechanical valves or biological valves are not deleterious to one's health, they both have their own limitations in that mechanical valves necessitate the lifelong use of anticoagulants while biological valves are susceptible to structural degradation and reoperation. Thus, in situ (in its original position or place) tissue engineering of heart valves serves as a novel approach that explores the use creating a living heart valve composed of the host's own cells that is capable of growing, adapting, and interacting within the human body's biological system.

Erin Baker Lavik is a professor of chemical, biochemical, and environmental engineering at the University of Maryland, Baltimore County. Lavik develops polymers and nanoparticles that can protect the nervous system. She is a Fellow of the American Institute for Medical and Biological Engineering.

<span class="mw-page-title-main">Milica Radisic</span> Serbian Canadian tissue engineer

Milica Radisic is a Serbian Canadian tissue engineer, academic and researcher. She is a professor at the University of Toronto’s Institute of Biomaterials and Biomedical Engineering, and the Department of Chemical Engineering and Applied Chemistry. She co-founded TARA Biosystems and is a senior scientist at the Toronto General Hospital Research Institute.

References

  1. ↑ Mahmoudi M, Yu M, Serpooshan V, Wu JC, Langer R, Lee RT, Karp JM, Farokhzad OC (2017). "Multiscale technologies for treatment of ischemic cardiomyopathy". Nature Nanotechnology. 12 (9): 845–855. doi:10.1038/nnano.2017.167. PMC   5717755 . PMID   28875984.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 Fliesler, Nancy (30 September 2011). "Could Nanotechnology Improve Treatment of Heart Attack and Heart Failure?". Mass Device. Retrieved 2019-04-11.
  3. 1 2 3 4 Heffernan NJ, Murthy N (2005). "Polyketal nanoparticles: A new pH-sensitive biodegradable drug delivery vehicle". Bioconjugate Chemistry. 16 (6): 1340–1342. doi:10.1021/bc050176w. PMID   16287226.
  4. ↑ Fu K, Pack DW, Klibanov AM, Langer R (2000). "Visual evidence of acidic environment within degrading poly-(lactic-co-glycolic acid) (PLGA) microspheres". Pharm. Res. 17 (1): 100–106. doi:10.1023/A:1007582911958. PMID   10714616. S2CID   22378621.
  5. 1 2 Looi YH, Grieve DJ, Siva A, Walker SJ, Anilkumar N, Cave AC, Marber M, Monaghan MJ, Shah AM (2008). "Involvement of Nox2 NADPH oxidase in adverse cardiac remodeling after myocardial infarction". Hypertension. 51 (2): 319–325. CiteSeerX   10.1.1.539.7577 . doi: 10.1161/hypertensionaha.107.101980 . PMID   18180403.
  6. ↑ Krijnen PA, Meischl C, Hack CE, Meijer CJ, Visser CA, Roos D, Niessen HW (2003). "Increased Nox2 expression in human cardiomyocytes after acute myocardial infarction". Journal of Clinical Pathology. 56 (3): 194–199. doi: 10.1136/jcp.56.3.194 . PMC   1769897 . PMID   12610097.
  7. 1 2 3 Somasuntharam I, Boopathy AV, Khan RS, Martinez MD, Brown ME, Murthy N, Davis ME (2013). "Delivery of Nox2-NADPH oxidase siRNA with polyketal nanoparticles for improving cardiac function following myocardial infarction". Biomaterials. 34 (31): 7790–7798. doi:10.1016/j.biomaterials.2013.06.051. PMC   3766948 . PMID   23856052.
  8. 1 2 Sheshadri G, Sy JC, Brown M, Dikalov S, Yang SC, Murthy N, Davis ME (2010). "The delivery of superoxide dismutase encapsulated in polyketal microparticles to rat myocardium and protection from myocardial ischemia-reperfusion injury". Biomaterials. 31 (6): 1372–1379. doi:10.1016/j.biomaterials.2009.10.045. PMC   2813932 . PMID   19889454.
  9. ↑ Khaper N, Kaur K, Li T, Farahmand F, Singal PK (2003). "Antioxidant enzyme gene expression in congestive heart failure following myocardial infarction". Molecular and Cellular Biochemistry. 251 (1–2): 9–15. doi:10.1023/A:1025448908694. PMID   14575298. S2CID   2610363.
  10. 1 2 3 Sy JC, Sheshadri G, Yang SC, Brown M, Oh T, Dikalov S, Murthy N, Davis ME (2008). "Sustained release of a p38 inhibitor from non-inflammatory microspheres inhibits cardiac dysfunction". Nature. 7 (11): 863–869. doi:10.1038/nmat2299. PMC   2705946 . PMID   18931671.

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