The ‘nanosponges’ – biodegradable polymer cores coated in human lung cell and immune cell membranes – can attract and neutralise the SARS-CoV-2 virus in cell culture, causing the virus to lose its ability to hijack host cells and reproduce.
The particles were developed by engineers at the University of California (UC) San Diego and tested by researchers at Boston University in Massachusetts.
In lab experiments, both the lung cell and immune cell types of nanosponges caused the SARS-CoV-2 virus to lose nearly 90% of its ‘viral infectivity’ in a dose-dependent manner. Viral infectivity is a measure of the ability of the virus to enter the host cell and exploit its resources to replicate and produce additional infectious viral particles.
Instead of targeting the virus itself, the nanosponges are designed to protect the healthy cells the virus invades.
“Traditionally, drug developers for infectious diseases dive deep on the details of the pathogen in order to find druggable targets. Our approach is different. We only need to know what the target cells are. And then we aim to protect the targets by creating biomimetic decoys,” said Liangfang Zhang, a nanoengineering professor at UC San Diego.
His lab first created the biomimetic nanosponge ‘platform’ more than a decade ago and has been developing it for a wide range of applications. When the novel coronavirus appeared, the idea of using the nanosponge platform to fight it came to Zhang "almost immediately," he said.
In addition to the encouraging data on neutralising the virus in cell culture, the researchers note that nanosponges cloaked with fragments of the outer membranes of macrophages could have an added benefit: soaking up inflammatory cytokine proteins, which are implicated in some of the most dangerous aspects of Covid-19 and are driven by immune response to the infection.
Each Covid-19 nanosponge – a thousand-times smaller than the width of a human hair – consists of a polymer core coated in cell membranes extracted from either lung epithelial type II cells or macrophage cells. The membranes cover the sponges with all the same protein receptors as the cells they impersonate, which inherently includes whatever receptors SARS-CoV-2 uses to enter cells in the body.
At a concentration of 5mg per millilitre, the lung cell membrane-cloaked sponges inhibited 93% of the viral infectivity of SARS-CoV-2. The macrophage-cloaked sponges inhibited 88% of the viral infectivity.
“From the perspective of an immunologist and virologist, the nanosponge platform was immediately appealing as a potential antiviral because of its ability to work against viruses of any kind,” said co-first author Anna Honko from Boston University. “This means that as opposed to a drug or antibody that might very specifically block SARS-CoV-2 infection or replication, these cell membrane nanosponges might function in a more holistic manner in treating a broad spectrum of viral infectious diseases.
“I was optimistically sceptical initially that it would work, and then thrilled once I saw the results and it sunk in what this could mean for therapeutic development as a whole.”
In the next few months, the UC San Diego researchers and collaborators will evaluate the nanosponges' efficacy in animal models. The UC team has already shown short-term safety in the respiratory tracts and lungs of mice.
“Another interesting aspect of our approach is that even as SARS-CoV-2 mutates, as long as the virus can still invade the cells we are mimicking, our nanosponge approach should still work. I'm not sure this can be said for some of the vaccines and therapeutics that are currently being developed,” said Zhang.
The researchers also expect these nanosponges would work against any new coronavirus or even other respiratory viruses, including whatever virus might trigger the next respiratory pandemic.
The COVID-19 nanosponge platform has significant testing ahead of it before scientists know whether it is safe and effective in humans, said Zhang. If the sponges reach the clinical trial stage there are multiple potential ways of delivering the therapy, including direct delivery into the lung for intubated patients, via an inhaler-like device for asthmatic patients, or intravenously, especially to treat the complication of cytokine storm.
A therapeutic dose could flood the lung with a trillion or more tiny nanosponges that could draw the virus away from healthy cells. Once the virus binds with a sponge, “it loses its viability and is not infective anymore, and will be taken up by our own immune cells and digested,” said Zhang.
The research was published in Nano Letters.
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