Monocyte Membrane-Fused Liposomes for Enhanced Targeted Treatment of Mesangioproliferative Glomerulonephritis

The rising incidence of end-stage renal disease, with mesangioproliferative glomerulonephritis (MsPGN) as a major contributor, underscores the urgent need for safe and effective therapeutic strategies. In this study, we developed monocyte membrane-fused liposomes loaded with celastrol (M-Lipo@CLT) to exploit the innate inflammatory homing capacity of monocytes for precise glomerular targeting. The monocyte-derived membrane functioned both as a targeting component and as a reservoir enabling active inflammation-specific drug delivery, thereby enhancing selective drug accumulation at diseased glomeruli. M-Lipo@CLT were fabricated via thin-film hydration followed by membrane extrusion, yielding uniform spherical nanoparticles with an average diameter of 80.0 ± 5.3 nm, a polydispersity index of 0.155 ± 0.050, and a zeta potential of -11.89 ± 1.5 mV. <i>In vitro</i>, M-Lipo@CLT demonstrated markedly increased cellular uptake, particularly under inflammatory conditions, in both RAW264.7 macrophages and HBZY-1 mesangial cells, confirming their inflammation-targeting capability. <i>In vivo</i>, employing a rat Thy1.1 MsPGN model, M-Lipo@CLT achieved superior renal and glomerular accumulation compared with conventional liposomes, leading to significant inhibition of mesangial cell proliferation, attenuation of renal inflammation, and preservation of glomerular architecture. Furthermore, safety assessments revealed substantially reduced systemic toxicity relative to free celastrol, highlighting the improved biocompatibility and minimized off-target effects of the formulation. Collectively, these results established M-Lipo@CLT as a promising glomerulus-targeted nanomedicine with enhanced efficacy and improved safety, offering a potential strategy for the treatment of MsPGN and other inflammation-driven diseases.