Nanosponges to treat coronavirus infection
Nanoparticles hidden in the human lung cell membrane and human immune cell membranes can attract and counteract the SARS-CoV-2 virus in cell culture, causing the virus to lose its capacity to attack host cells and replicate.
Engineers at the University of California San Diego and developed the “nanosponges” and were screened by scientists at Boston University to treat coronavirus infection.
The researchers from UC San Diego call their nanoparticles as “nanosponges” due to the fact that they soak up the harmful viruses and toxic substances.
In a dose-dependent manner, both the immune cell and lung cell types of nanosponges made the novel coronavirus to lose around 90% “viral infectivity”, in laboratory examinations. The measure of the capability of the virus to enter the host cell and replicate exploiting its sources and produce more infectious viral fragments is called viral infectivity.
These nanosponges are made to protect the healthy cells from the virus attacks, instead of targeting the virus, which can also be used to treat coronavirus infection.
Liangfang Zhang, nanoengineering professor, the UC San Diego Jacobs School of Engineering said, “Generally, in order to find druggable targets, drug designers for infectious diseases dive deep on the details of the pathogen. Our strategy is different from others. To identify what the target cells are is the only need. And later on, by producing biomimetic decoys we focus to protect the targets”.
Initially, this biomimetic nanosponge platform was developed by his laboratory more than a decade ago and also has been developing it for a vast array of applications since then. He added, the thought of using the nanosponge to fight COVID-19 came to Zhang “almost immediately” when the novel coronavirus pandemic started.
The scientists found that nanosponges masked with fragments of the outer membranes of macrophages could have an additional advantage: taking in inflammatory cytokine proteins, which are implicated in several of the most dangerous aspects of COVID-19 and are driven by an immune response to the virus, along with the encouraging data on neutralizing the virus in cell culture.
COVID-19 nanosponges: Developing and Testing
Thousand times smaller than the width of a human hair – the COVID-19 nanosponge – includes a polymer core covered in cell membranes drawn out either from macrophages or lung epithelial type II cells. The nanosponges are covered with the membranes with all the same protein receptors as the cells they impersonate – and this inherently comprises the receptors coronavirus uses to invade the host.
To test against the novel coronavirus the scientists prepared nanosponges in solution in a number of different concentrations. The UC San Diego scientists relied on a group at Boston University’s National Emerging Infectious Diseases Laboratories (NEIDL) to carry out independent examinations, to test the capability of the nanosponges to obstruct SARS-CoV-2 infectivity. The scientists, led by Anthony Griffiths, associate professor of microbiology at Boston College School of Medicine, examined the capacity of numerous concentrations of each nanosponge type to reduce the infectivity of live SARS-CoV-2 virus in BSL-4 laboratory – the highest possible biosafety degree for a research study center, the same strain are being tested in various other COVID-19 therapeutic and vaccination studies.
The lung cell membrane-cloaked sponges hindered 93% of the viral infectivity of SARS-CoV-2, at a concentration of 5 milligrams per milliliter. 88% of the viral infectivity of SARS-CoV-2 was inhibited by the macrophage-cloaked sponges.
Anna Honko, a co-first author on the paper and a Research Associate Professor, Microbiology, Boston University’s NEIDL, said “The nanosponge platform was immediately appealing as a potential antiviral from the point of view of an immunologist and virologist, due to its ability to work against viruses of any type. As opposed to an antibody or drug that might specifically block infection or duplication of SARS-CoV-2, this study suggests that these cell membrane nanosponges might function in a more natural way in treating a wide range of viral infections. I was favorably cynical at first that it would certainly work, and afterward delighted as soon as I saw the outcomes and it sunk in what this might imply for restorative development as a whole”.
The UC San Diego scientists as well as partners will certainly evaluate the efficacy of nanosponges in animal models, in the following few months. The UC San Diego group has already shown temporary safety in the mice’s respiratory systems and lungs. The scientists are moving as fast as feasible, however, if and when these COVID-19 nanosponges will certainly be tested in humans depends upon a range of factors.
Zhang added, “An additional fascinating element of our strategy is that our nanosponge approach should still function even as the novel coronavirus mutates, as long as the virus can still invade the cells we are mimicking”. He also included that he is unsure this can be stated for several of the vaccines, and therapies that are being developed presently.
Additionally, the researchers expect these nanosponges would certainly antagonize any new coronavirus or even any other respiratory viruses.
Mimicking immune cells and lung epithelial cells
As the first step in COVID-19 infection, the novel coronavirus infects lung epithelial cells, Zhang and his colleagues reasoned that it would certainly make sense to mask a nanoparticle in fragments of the outer membranes of lung epithelial cells to see instead of lung cells if the infection could be deceived into latching on it.
Zhang and colleagues created a 2nd sponge cloaked in macrophage membrane because the macrophages, which are white blood cells that play a significant role in inflammation, also are extremely active in the lung throughout the course of a COVID-19.
To study whether the macrophage sponges additionally have the ability to silent cytokine storms in patients with COVID-19 is an ongoing plan by the researchers.
Zhang said, “We will see if the macrophage nanosponges can neutralize the virus and reduce the effects of the excessive quantity of these cytokines”.
To establish therapies for sepsis utilizing macrophage nanosponges utilizing macrophage cell fragments as cloaks build on years of work.
Zhang and a group of researchers at UC San Diego revealed that macrophage nanosponges can safely counteract both endotoxins and pro-inflammatory cytokines in the bloodstream of mice, in a paper published in 2017 in Proceedings of the National Academy of Sciences. Cellics Therapies – a biotechnology company based in San Diego co-founded by Zhang is working to translate this macrophage nanosponge work into the clinic.
Zhang warned that the possible COVID-19 therapeutic – the COVID-19 nanosponge system has considerable testing ahead of it before the scientists understand whether it would be safe as well as reliable therapy in humans against the COVID-19. However, if the nanosponges get to the clinical trial phase, there are several prospective methods of supplying the treatment that including direct delivery into the lungs for intubated patients, intravenously, particularly to deal with the problem of the cytokine storm or via an inhaler like for asthmatic patients.
Zhang stated a therapeutic dose of nanosponges could attract the virus far from healthy cells by flooding the lung with a trillion or even more nano-sized sponges. “It loses its feasibility and is not infective anymore as soon as the infection binds with a sponge, and will be captured by our own immune cells and digest them”.
Zhang added, “The potential for preventative therapy could be seen, for a restorative that could be provided early due to the fact that once the nanosponges enter the lung, they can stay in the lung a while”. “If there are nanosponges waiting for destroying it, the virus could be blocked”.
Growing momentum for nanosponges
The first membrane-cloaked nanoparticles were developed by Zhang’s laboratory at UC San Diego over a decade earlier. With fragments of RBC membranes, the first of these nanosponges were masked. These nanosponges are being established to treat bacterial pneumonia and Cellics Therapeutics have carried out all phases of pre-clinical screening. Currently, the firm is in the process of submitting the investigational new drug application to the FDA for its lead prospect for treating methicillin-resistant Staphylococcus aureus pneumonia using RBC nanosponges. The first patients in a medical trial will be dosed the following year as per the company’s estimate.
The researchers from UC San Diego have additionally revealed that nanosponges can deliver medicines to a wound site; sop up bacterial toxic substances that cause sepsis, and obstruct HIV prior to it can infect T cells in humans.
These nanosponges have the standard building for each: To make sure that it might be disguised as a platelet, or an immune T cell or an RBC – a biodegradable, FDA-approved polymer core coated in a particular kind of cell membrane. The masking keeps the body’s immune system from identifying and killing the particles as unsafe intruders.
Zhang claimed, “I think of the active components in the cell membrane fragments. This is a different method of looking at drug advancement”. “I hope various other groups develop risk-free as well as reliable therapies and vaccines for For COVID-19 as soon as possible. Simultaneously, we are working and intending as if the globe is counting on us”.
The initial information explaining this new direction for “Nanosponges to treat coronavirus infection” was released in the journal Nano Letters on June 17.