DON’T GO BREAKING MY HEART
Heart disease is the second leading cause of death in Canada and the leading cause of death among noncommunicable diseases. As of 2020, approximately 2.4 million Canadians have heart disease, a number that doesn’t seem likely to decrease any time soon.
However, a new study from a U of O faculty of medicine research team, suggests that sprayable gold nanoparticles could be an effective therapy for restoring cardiac function after a heart attack. The study was led by Dr. Emilio Alarcon and Dr. Erik Suuronen, and performed by Dr. Marcelo Muñoz and PhD candidate Cagla Eren Cimenci.
Muñoz, a pharmacist, chemist, researcher at the University of Ottawa Heart Institute and one of the leading researchers on this study, sat down with the Fulcrum to discuss his work.
What is Myocardial Infarction (MI)?
According to Dr. Muñoz, a myocardial infarction, also known as a heart attack, occurs when a lack of blood flow prevents the heart from receiving any oxygen and nutrients. Usually, this occurs due to clogged coronary arteries, which are responsible for supplying the heart with blood and nutrients. If this issue is not resolved “in minutes, no more than 30 minutes, that area of the heart will be permanently damaged, and it will not recover,” said Muñoz.
Although a person can survive an MI, the damage causes the heart to lose two important functions: muscle contractility and myocardial electrical conductivity. Muscle contractility refers to the heart’s ability to contract or tense with enough force to pump blood. Electrical conductivity refers to the heart’s ability to conduct electrical signals, which cause the heart to contract and maintain a steady beat.
Muñoz added that these two functions are highly related, “so you lose conductivity, you lose contractility so that in the future, it gets worse and worse and turns into heart failure, which is a disease that doesn’t have any cure.”
The research team used gold nanoparticles with a custom peptide cap and miniature spray nozzle, to create a spray that was directly applied to the hearts of mice after experiencing myocardial infarctions. The spray was applied seven days after the mice experienced induced-MI because this is when scar tissue began to form in the heart at mouse level, which the researchers identified as a “prime opportunity to intervene to limit pathological cardiac remodeling and promote infarct repair”.
When asked why the group chose to use gold, Muñoz enthusiastically explained, “Gold is beautiful because it has such amazing properties. First, it is super stable and really unreactive.”
Other metals are processed and changed by the body, which would make it difficult to observe their effect on the body. “But the advantage of gold as our metal is that if you are putting metallic nanoparticles into the system, broadly, they will stay small metallic nanoparticles when they spread.”
However, the group did have to address one disadvantage of using gold, “the gold nanoparticles are toxic in high concentrations. So, what was the trick here? We designed a tiny micro nozzle that we developed to deliver the therapy directly into the heart.”
The use of the optimized nozzle ensured that the spray was localized to the area that is affected by the heart attack, rather than being applied to a larger area and unnecessarily increasing the amount of gold in the body. It also ensured an even amount of the spray was applied to the entire affected area of the heart.
The group used custom peptides to stabilize the gold, a technique that was based on previous studies of stabilizing nanosilver. The peptides are a short chain of amino acids that were used to cap the nanogold to stabilize it.
“Gold particles have a tendency to aggregate and are easily recognized by the immune system and it generates more toxicity. So we developed a peptide system that is able to cap the gold particles and keep the gold nanoparticles stable over time, making it ideal for delivering when we spray the heart and it stays a gold nanoparticle,” said Muñoz.
Muñoz explained mice were the perfect test species because their physiological proportions are similar to humans and can be extrapolated during research. Mice are also cost-effective, easy to access, easy to work with, and provide a good starting point during research that may involve future testing on larger animals.
What were the results?
The researchers observed improvement in cardiac function and electrical signal conduction in the mice that were given the spray, and the results were able to be replicated in repeated experiments.
The team is currently seeking funding to perform future experiments on larger animals. They plan to test this treatment as a minimally invasive treatment on pigs or rabbits, but their main goal is to eventually use this therapy to treat heart failure.
The researcher added, “If we can mimic the treatment that we apply in this research, and we scale it up to humans, hopefully in the future, if for some reason you can’t attend an emergency room this will be applied after two weeks and still be able to recover your cardiac functionality.”
Muñoz praised his team for their hard work and collaboration. In addition, he hoped, “this treatment will turn into a real therapy, because it will be a step forward in the treatment of heart failure.”