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: Polyclonal antibodies

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 the capacity to widely inhibit pathogenic polyclonal antibody reactions. Further modification of D-ALW using PEG-PLGA nanoparticles enhance good kidney-targeting ability extend half-life. Here, we demonstrate that maintains higher binding inhibition efficiencies achieves stability. Most importantly, exhibit excellent prolong half-life peptides BALB/c mice. Additionally, compared significantly reduce glomerular deposition IgG C3, improve renal histopathologies, such as proliferation inflammatory cells infiltration, markedly lifespan MRL/lpr lupus-prone Overall, these results establish offer synergistic benefits both safety efficacy, providing long-term preservation treatment advantages nephritis.