Anti-DNA antibody-targeted D-peptide nanoparticles ameliorate lupus nephritis in MRL/lpr mice

• DOI: 10.1016/j.jaut.2024.103205
• Publication Date: 2024-03-16T07:37:49Z
• Authors: Yaqi Wang; Shuang Wang; Wei Liu; Hanjiang Gu; Mai Luo; Tong Xiao; Mingzhu Zhou; Yutong Ran; Shengxiang Xiao; Yumin Xia; Huixia Wang
• Keywords: Mice, Inbred MRL lpr; Mice; Disease Models, Animal; Mice, Inbred BALB C; Antibodies, Antinuclear; Immunoglobulin G; Animals; Nanoparticles; Humans; Female; Kidney; Peptides; Lupus Nephritis

Peptide ALW (ALWPPNLHAWVP) targeting anti-dsDNA antibodies has shown promising therapeutic effects in alleviating lupus nephritis, but is potentially limited by poor stability and non-kidney targeting. We recently developed a D-form modified ALW, called D-ALW, which has the capacity to widely inhibit pathogenic polyclonal anti-dsDNA antibody reactions. Further modification of D-ALW using PEG-PLGA nanoparticles to enhance good kidney-targeting ability and extend half-life. Here, we demonstrate that the D-form modified ALW maintains higher binding and inhibition efficiencies and achieves higher stability. Most importantly, D-ALW nanoparticles exhibit excellent kidney-targeting ability and prolong the half-life of the peptides in BALB/c mice. Additionally, compared to D-ALW, D-ALW nanoparticles significantly reduce the glomerular deposition of IgG and C3, improve renal histopathologies, such as glomerular proliferation and inflammatory cells infiltration, and markedly prolong lifespan in MRL/lpr lupus-prone mice. Overall, these results establish that the D-ALW nanoparticles offer synergistic benefits in both safety and efficacy, providing long-term renal preservation and treatment advantages in lupus nephritis.