Mesangial proliferative glomerulonephritis (MsPGN),one of the most common glomerulonephritis pathological types,often leads to end-stage renal disease over a prolonged period.But the current treatment of MsPGN is non-specific and causes serious side effects,thus novel therapeutics and targeting strategies are urgently demanded.By combining the advantages of PEG-PLGA nanoparticles and the size selection mechanism of renal glomerulus,we designed and developed a novel PEG-PLGA nanoparticle delivery system capable of delivering dexamethasone acetate (A-DEX) into glomerular mesangium.We determined that 90 nm was the optimum size to encapsulate A-DEX for glomerular mesangium targeting based on the size-selection mechanism of glomerulus.After intravenous administration in rats,90 nm DiD-loaded NPs were found to accumulate to a greater extent in the kidney and kidney cortex compared with the free DiD solution.The 90 nm A-DEX NPs are also more stable at room temperature and showed a sustained release patte.In rat glomerular mesangial cells (HBZY-1) in vitro,we found that the uptake of 90 nm A-DEX NPs was both temperature-dependent and energe-dependent,and they were mostly engulfed via clathrin-dependent endocytosis pathways.In summary,we have successfully developed a glomerular mesangium-targeted PEG-PLGA NPs,which is potential for the treatment of MsPGN.