Kidney functional stages influence the role of PEG end-group on the renal accumulation and distribution of PEGylated nanoparticles

Modification with polyethylene glycol (PEG), or PEGylation, has become a popular method to improve the efficiency of drug delivery in vivo using nanoparticle-based delivery systems. The PEG end-group plays an important role in the in vivo fate of PEGylated nanoparticles through its interactions with proteins in the serum and the cell membrane. However, the effects of PEG end-groups on the renal clearance of PEGylated nanoparticles remain unclear. Kidney function may also affect the renal accumulation and distribution of nanoparticles. Herein, we demonstrate that the accumulation and distribution of PEGylated nanoparticles in kidneys are significantly affected by both the PEG end-group and kidney function damage. Interestingly, compared to PEG with an amino or methoxy end-group, PEG with maleimide as the end-group markedly enhanced the accumulation of PEGylated nanoparticles in normal kidneys, which may improve renal clearance. However, obvious enhancements in the renal accumulation and medullary distribution of PEGylated nanoparticles are detected in kidneys with functional impairment. Damage to renal function further affects how the PEG end-group influences the accumulation and distribution of PEGylated nanoparticles in kidneys in vivo. Collectively, the findings provide deep insights into the interactions between PEGylated nanoparticles and kidneys in vivo.