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Nanosponges sop up toxins and help repair tissues

Tiny particles coated with cell membranes can do more than deliver drugs

NANOHEALERS A single nanosponge (large sphere in this illustration) can trap toxins produced by a variety of pathogens.

To take his fledgling lab to new heights, Liangfang Zhang hatched a plan that he considered brilliant in its simplicity. It involved procedures that many of his peers found a little out there. But if he could make his idea work, it would clear a major hurdle to safely ferry therapies through the body on nanoparticles one-thousandth the width of a human hair. Yet back in 2010, the young nanoengineer could not convince the National Institutes of Health, the main funder of U.S. biomedical research, to support the project. Zhang applied for funding four or five times over several years, to no avail.

“It felt quite lonely,” he says. “But I just felt this is very unique stuff. And it may become a big thing.” Pulling funds from other projects and from the start-up package he received to set up his lab at the University of California, San Diego, Zhang did the experiments for his breakthrough paper, published in 2011 in the Proceedings of the National Academy of Sciences. He and coworkers created a new class of nanoparticles, made from carbon-containing polymers, that could slip through blood vessels in a mouse without triggering an immune reaction. While immune responses are important for killing disease-causing pathogens, the same reactions are a nuisance when they clear out molecules made to deliver lifesaving drugs. Then, instead of just viewing their particles as a drug-delivery system, which most other researchers were focused on, Zhang and his team made a surprising pivot. They repurposed the particles to act as “nanosponges” that trap and remove toxins from the blood. In lab experiments, the nanosponges worked against toxins unleashed by E. coli and some of the harder-to-fight bacteria. Nanosponges also slowed harmful inflammation in mice with a form of rheumatoid arthritis and diverted HIV and Zika from the cells those viruses normally infect, the researchers reported last year.

Nanosponges, which have not yet been tested in people, do their under-the-radar cleanup because of an offbeat idea: The synthetic nanoparticles are coated with membranes from living cells, which helps them blend in. And a single nanosponge can root out a slew of mischief-makers without knowing much about them individually. Many toxins that attack red blood cells, for example, will cling instead to nanoparticles coated with bits of those very cells. Zhang’s team at UC San Diego and others have created a growing arsenal of nanosponges cloaked in membranes of red or white blood cells, each of which absorbs its own set of toxins. Zhang’s work “opened up the whole field” of membrane-coated nanoparticles, says Omid Farokhzad, a physician-scientist at Brigham and Women’s Hospital in Boston who studies nanoparticles as medicine (SN: 11/11/16, p. 22). Many labs are now “building on the platform that Zhang’s group developed.”

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