Nanoparticles carry tumour-fighting drugs

SCIENTISTS have found a way to sneak nanoparticles carrying tumour-fighting drugs past cells of the immune system, which would normally engulf the particles, preventing them from reaching their target. The technique takes advantage of the fact that all cells in the human body display a protein on their membranes that functions as a specific ‘passport’ in instructing immune cells not to attack them. By attaching a small piece of this protein to nanoparticles, scientists were able to fool immune cells in mice into recognizing the particles as ‘self’ rather than foreign, thereby increasing the amount of medication delivered to tumours.

National Institute of Biomedical Imaging and Bioengineering (NIBIB) grantee, Dr Dennis Discher, a molecular and cell biophysicist in Chemical and Biomolecular Engineering at the University of Pennsylvania has published a paper in in which he describes a new method developed by his lab that helps nanoparticles escape attacks from cells of the immune system, specifically macrophages.

Cancer nanotechnology

Current approaches to chemotherapy leave patients with severe side effects because anti-cancer drugs meant to destroy tumours inadvertently kill healthy cells in the body. But scientists have recently developed nanoparticles that can ferry toxic medications directly to tumours while sparing healthy tissue. Because of their small size, nanoparticles escape from leaky blood vessels that are characteristic of tumours and accumulate in the cancerous tissue. Tumour cells take up the particles which release their toxic contents once inside. This localized delivery system allows doctors to give patients higher doses of medications than would normally be tolerated.

Previous attempts have been made to ward off attack by the immune system by coating nanoparticles densely with polyethylene glycol (PEG) “brushes” that physically block the adhesion of proteins that normally deposit onto foreign bodies to attract macrophages. While these brushes delay the onset of the immune response, they don’t prevent it.

The inspiration for Dr Discher’s breakthrough work dates back thirteen years when a group of researchers showed with genetically engineered mice that a protein called CD47—which is found in the cell membranes of nearly all mammals—interacts with a receptor on macrophages called SIRPa, and, in doing so, signals that the cell is native and shouldn’t be destroyed. The findings hinged on deleting mouse CD47 and raised many questions, including how such mice survive and whether there was relevance to humans.

Dr Discher, who was engineering nanoparticles that self-assemble into various shapes at the time of the discovery, realized that the CD47-SIRPa mechanism for self-recognition could, in principle, be exploited to help nanoparticles sneak past the immune system. But it was also clear that human versions of purified proteins needed to be studied for any translation to humans.

In 2008, Dr Discher’s lab demonstrated that human CD47 acts similarly to mouse CD47 as a “marker of self” via signalling through the SIRPa receptor. Shortly thereafter, a group oMiesten kengät laajasta valikoimasta