In 2011, Nanoengineer Liangfang Zhang 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. This was great because although immune responses are important for killing disease-causing pathogens, they are a nuisance when they clear out molecules made to deliver lifesaving drugs.
Then, the team decided to try something new. Instead of just viewing their particles as a drug-delivery system, they repurposed the particles to act as “nanosponges” that trap and remove toxins from the blood. They conducted lab experiments to test their nanosponges. They were able to get them to work against toxins unleashed by E. coli and some of the harder-to-fight bacteria. In addition, they slowed harmful inflammation in mice with a form of rheumatoid arthritis and diverted HIV and Zika from the cells those viruses normally infect. They have not yet been tested in people.
How They Work
- The synthetic nanoparticles are able to accomplish their under-the-radar cleanup because they are coated with membranes from living cells, which helps them blend in.
- A single nanosponge can root out numerous different kinds of toxins. This is because many toxins that attack red blood cells will cling instead to the nanoparticles coated with bits of those very cells.
The More The Merrier
Che-Ming Jack Hu, the graduate student in Zhang’s lab who took on the project, said that the concept of cloaking a human-made particle with bits of unpredictable biological membranes “was very unorthodox” at the time. Zhang’s team at UC San Diego pioneered this approach but since then, others too have joined in. Together, the different teams 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.
These nanosponges do more than just act as camouflage for the nanoparticles. Their coatings are able to trap toxins. Hu said that toxins “like to poke holes in red blood cells.” So their Ingenious design makes it so if toxins go after the nanoparticles, the toxins “get stuck” on the nanoparticles’ membranes and can no longer harm cells. Instead, the troublemakers are carried to the liver and broken down, problem solved.
Recent studies include:
- In a 2017 mouse study in the Proceedings of the National Academy of Sciences, macrophage-coated particles trapped and rendered powerless some of the molecules that drive inflammation leading to sepsis, an uncontrolled response to infection that kills about 6 million people worldwide each year.
- Last September, the team reported in Nature Nanotechnology that neutrophil nanosponges sop up toxins that cause rheumatoid arthritis in mice.
- In lab dish experiments reported in November in Advanced Materials, nanosponges coated with T cells diverted HIV from actual T cells, the cells this virus typically attacks, eventually causing AIDS.
Potential Targets
The list of nanosponges being tested in lab dishes and mouse studies is getting longer every year. Here are a few targets being explored:
(The type of nanosponge coating is in parentheses.)
Bacterial Infections
- Sepsis (red blood cell, macrophage)
- Pneumonia (red blood cell)
Skin And Soft Tissue
- Infection (red blood cell)
Viral Infections
- HIV (CD4 T cell)
- Zika (mosquito host cell)
- Influenza (red blood cell)
Autoimmune diseases
- Rheumatoid arthritis (neutrophil)
- Autoimmune hemolytic anemia (red blood cell)
- Immune thrombocytopenic purpura (platelet)
Venom
- From snakes and other animals (red blood cell, white blood cell, platelet)
Conclusion
For now, Zhang’s biotech start-up, Cellics Therapeutics, hopes to launch a patient study with the red blood cell nanosponges. At the top of the list of about a dozen conditions that could make good targets for the nanosponges are sepsis and pneumonia.
