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The Stealth Properties of PEG-Coated Nanoparticles are Dependent on the PEG Grafting Densities

The Lai lab at UNC Chapel Hill published an article in Molecular Pharmaceiuticals – Evading Immune Cell Uptake and Clearance Requires PEG Grafting at Densities Substantially Exceeding the Minimum for Brush Conformation. Mol. Pharmaceutics, 2014, 11 (4), pp 1250–1258, DOI: 10.1021/mp400703d.

Exploration in PEG Grafting

This paper critically pointed out: Coating nanoparticles with polyethylene glycol (PEG), which reduces particle uptake and clearance by immune cells, is routinely used to extend the circulation times of nanoparticle therapeutics. Nevertheless, due to technical hurdles in quantifying the extent of PEG grafting, as well as in generating very dense PEG coatings, few studies have rigorously explored the precise PEG grafting density necessary to achieve desirable “stealth” properties.

Here, using polymeric nanoparticles with precisely tunable PEG grafting, we found that, for a wide range of PEG lengths (0.6-20 kDa), PEG coatings at densities substantially exceeding those required for PEG to adopt a “brush” conformation are exceptionally resistant to uptake by cultured human macrophages, as well as primary peripheral blood leukocytes. The stealth properties of PEG-coated nanoparticles are critically dependent on achieving PEG grafting at densities exceeding those required for brush conformation.


Creative PEGWorks offers novel PEGylation reagents and highly reactive PEG derivatives to achieve high-density PEG grafting on the surface of nanoparticles, microparticles, biochips, etc.