New information on how to design nanoparticles that avoid macrophage uptake

Few researchers doubt the potential for nanoparticles to revolutionize the way anticancer drugs and imaging agents are delivered to tumors.

Nonetheless, one major limitation that investigators still must overcome to fully realize that promise is the propensity for immune cells such as macrophages to engulf and eliminate nanoparticles circulating in the bloodstream. Now, findings published in the journal Langmuir should provide scientists with better information on how to design nanoparticles that avoid macrophage uptake.

Michael Pishko, Ph.D., led a team of investigators who studied the effect of various surface coatings and compositions on macrophage uptake of layered nanoparticles. The researchers found that nanoparticles coated with the biocompatible polymer poly(ethylene glycol), better known as PEG, had the lowest percentage of uptake by macrophages when compared to nanoparticles with either a negative or positive charge on their surfaces.

However, the investigators also found that not all PEG coatings are alike. PEG comes in a variety of sizes, and the researchers found that shorter and longer PEG molecules make better nanoparticle coatings, at least as far as minimizing macrophage uptake is concerned.

The researchers showed, too, that PEG does not discourage blood proteins from sticking to the nanoparticles, a finding contrary to the widely held hypothesis explaining how PEG reduces macrophage uptake. Instead, the researchers note, PEG appears to better control or modulate the building up of charge that can occur on a nanoparticle surface as proteins accumulate. The investigators propose that coatings that can keep changes in nanoparticles’ surface charge to a minimum will do a better job of hiding the nanoparticles from elimination by the immune system.

This work is detailed in a paper titled, “Macrophage uptake of core-shell nanoparticles surface modified with poly(ethylene glycol).” This paper was published online in advance of print publication. An abstract of this paper is available at the journal’s website. View abstract.