Nanoparticles are promising vectors for delivery of drugs to precise areas of the body, offering the ability to treat disease with limited side effects. Yet, our immune system is impressively robust and nanoparticles are attacked by it just like any other intruder, preventing the effectiveness of nanotherapies.
To overcome this challenge, researchers from The Methodist Hospital Research Institute used lipids and proteins from the very white cells of the immune system that would attack to coat nanoparticles for safe passage through the body. These so called “LeukoLike Vectors”, or LLVs, are nanoporous silicon particles that were coated with purified membranes harvested from leukocytes. Moreover, according to the study abstract “they can communicate with endothelial cells through receptor–ligand interactions, and transport and release a payload across an inflamed reconstructed endothelium.”
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Tasciotti and his group took metabolically active leukocytes (white blood cells) and developed a procedure to separate membranes from cell innards. By coating their nanoparticles with intact membranes in their native composition of lipids and proteins, the researchers created the first drug-carrying nanoparticles that look and act like cells — leukolike vectors.
“Using the membranes of white blood cells to coat a nanoparticle has never been done before,” Tasciotti said. “LLVs are half man-made — the synthetic silicon core — and half made of man — the cell membrane.”
Can the membrane be produced entirely via synthetic means?
“Being able to use synthetic membranes or artificially-created membrane is definitely something we are planning for the future,” Tasciotti said. “But for now, using our white blood cells is the most effective approach because they provide a finished product. The proteins that give us the greatest advantages are already within the membrane and we can use it as-is.”
As the technology is developed, Tasciotti said a patient’s own white cells could be harvested and used to create personalized LLVs.
To test whether the LLVs would be protected from macrophage sequestration and destruction, Tasciotti’s team tested LLVs coated with human membranes and found that human macrophages left the LLVs unharmed, thus confirming the preservation of the self-recognition principle.
“LLVs are dotted with proteins that help the particles reach specific targets, from inflamed or damaged tissues to cancer cells recruiting blood vessels,” Tasciotti said. “Over time the membrane lipids and proteins will break away, leaving the nanoparticles to degrade naturally after releasing their payload.”
The research team also looked at how well the drugs traveled through the LLV membrane. They found that rather than introducing an obstacle to drug release, the membrane provides controllable release of the drug once the nanoparticles reach their target tissue.
Press release: Nanoparticles that look and act like cells
Article in Nature Nanotechnology: Synthetic nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like functions