Anti-PEG antibodies enriched in the protein corona of PEGylated nanocarriers impact the cell uptake

Poly(ethylene glycol) (PEG) is the gold standard used to reduce unspecific protein adsorption and prolong nanocarrier circulation time. However, this stealth effect could be counteracted by the increasing prevalence of anti-PEG antibodies in the bloodstream. Up to now, the presence of anti-PEG antibodies in the protein corona and their effect on cell uptake has not been investigated yet. Our results showed a high concentration and prevalence of anti-PEG antibodies in the German population. PEGylated nanocarriers exhibited a higher level of anti-PEG antibodies in the protein corona compared to non-PEGylated, which lead to higher uptake in macrophages. Consequently, the anti-PEG antibodies in the protein corona could mitigate the stealth effect of PEG, leading to accelerated blood clearance and unwanted side effects.

Automated summary

Poly(ethylene glycol) (PEG) is commonly used to reduce unspecific protein adsorption and prolong nanocarrier circulation time, but the presence of anti-PEG antibodies in the bloodstream can counteract its stealth effect. This study found a high concentration and prevalence of anti-PEG antibodies in the German population, which led to higher uptake in macrophages and accelerated blood clearance of PEGylated nanocarriers.