Synergistic Therapeutic Effects of Stimuli Responsive Nanocomposites for Eculizumab Delivery on Membranous Glomerulonephritis

Membranous glomerulonephritis (MN) is clinically marked by significant proteinuria or nephrotic syndrome, and pathologically by a uniform thickening of the glomerular capillary basement membrane due to diffuse subepithelial immune complex deposition without notable cell proliferation. In this study, we synthesized a novel therapeutic agent, compound 1, designed for synergistic use with Eculizumab (Ecu) in MN treatment. To optimize the delivery and therapeutic effect of this combination, we developed an advanced composite drug carrier, mPEG-pHPMA@CP1@1@Ecu, incorporating methoxy polyethylene glycol (mPEG) and poly(2-hydroxypropyl methacrylamide) (pHPMA) with a metal-organic framework known as CP1. Structural and compositional integrity of this carrier was rigorously characterized. Our studies demonstrated that mPEG-pHPMA@CP1@1@Ecu could significantly mitigate hypoxia-induced renal tubular epithelial cell damage, highlighting the synergistic potential of compound 1 and Ecu. This new carrier system shows promising therapeutic potential for MN management.