Precision immunotherapy of moderate-to-severe atopic dermatitis mice using mycophenolate mofetil nanoparticles.

Abstract

Mycophenolate mofetil (MMF) shows significant potential for precision immunotherapy in moderate to severe atopic dermatitis (AD). However, its clinical application is limited by inadequate delivery efficiency and dose related toxicities. Herein, we propose a straightforward and effective drug delivery strategy that involves coating MMF with polydopamine (PDA) to fabricate MMF nanoparticles (MMF NPs). A systematic investigation of their therapeutic efficacy and mechanism of action was also conducted in the AD model mice. Due to surface hydrophilicity and nanoscale effects mediated by PDA, MMF NPs demonstrate excellent stability, high drug loading capacity, and optimized pharmacokinetics. The prolonged circulation time and enhanced permeability retention effect reduce both toxicity and susceptibility to infections associated with MMF, which leads to a marked improvement in the therapeutic efficacy of AD. Finally, MMF NPs achieve precise immunotherapy through the synergistic effect by balancing systemic immunity and precisely targeting the local inflammatory microenvironment. This study not only presents a safe and effective treatment strategy for AD but also introduces a novel delivery approach for the clinical application of MMF in immune-mediated disorders.