When nanoparticles are used to deliver drugs to specific parts of the body, they must avoid being mistaken for foreign pathogens by the immune system, which will attack and destroy them. This is a significant hurdle to overcome. Researchers in the US are working to better understand the body’s cellular defences and design nanoparticles that can evade them.  

The immune system relies on groups of white blood cells called macrophages, which seek out and consume any foreign invaders and diseased tissues that do not have the correct healthy proteins displayed on their surfaces. Macrophages form different sub-populations, or phenotypes, and each phenotype plays a distinctive role in protecting the body.  

Betty Kim and co-workers at the Mayo Clinic in the US recently published results of a study trialling nanoparticles that carry a special cancer-cell-derived ‘don’t-eat-me’ protein on their surface to help them evade macrophage phenotypes.  

The researchers divided the macrophage phenotypes into two broad categories; M1 macrophages — pro-inflammatory cells thought to target foreign invaders — and M2 macrophages, which work to modulate the overall immune system. Kim’s team incubated nanoparticles of three different sizes in culture trays together with groups of inactivated macrophages, M1, and M2 macrophages. Some of the nanoparticles were coated in long-chain polymers, while others weren’t. 

“We observed enhanced nanoparticle uptake by activated macrophages [compared to their inactivated counterparts],” write the researchers. More importantly, the team discovered that M1 macrophages particularly targeted the larger particles and consumed significantly more nanoparticles of all sizes compared to M2.  

The researchers replicated previous findings in which coated nanoparticles, particularly smaller ones, were partly protected from macrophage activity. They then decided to trial a method of modifying the nanoparticles’ surface by adding a ‘don’t-eat-me’ protein, called CD47, used by cancer cells to evade macrophages. CD47 works by binding to another protein on the macrophage surface, blocking its destructive activity.  

“We observed a large inhibition of uptake by M1 macrophages, suggesting that CD47 signalling appears to play a greater role in regulating M1 compared to M2,” write the researchers. The CD47 coating protected the larger nanoparticles significantly better than the long-chain polymers did.  

The team hope their insights will help scientists improve nanoparticle treatments for many different diseases.

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