Anti-DNA antibody-targeted D-peptide nanoparticles ameliorate lupus nephritis in MRL/lpr mice.
In: Journal of Autoimmunity, Jg. 145 (2024-05-01), S. N.PAG
Online
academicJournal
Zugriff:
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. • Poor stability and non-kidney targeting hampered the effect of peptide ALW. • D-ALW improves proteases resistance and binding affinity to anti-dsDNA antibodies. • D-ALW nanoparticles possessed high renal retention of peptide. • D-ALW nanoparticles largely prolonged the lifespan of MRL/lpr mice. [ABSTRACT FROM AUTHOR]
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Anti-DNA antibody-targeted D-peptide nanoparticles ameliorate lupus nephritis in MRL/lpr mice.
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Autor/in / Beteiligte Person: | Wang, Yaqi ; Wang, Shuang ; Liu, Wei ; Gu, Hanjiang ; Luo, Mai ; Xiao, Tong ; Zhou, Mingzhu ; Ran, Yutong ; Xiao, Shengxiang ; Xia, Yumin ; Wang, Huixia |
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Zeitschrift: | Journal of Autoimmunity, Jg. 145 (2024-05-01), S. N.PAG |
Veröffentlichung: | 2024 |
Medientyp: | academicJournal |
ISSN: | 0896-8411 (print) |
DOI: | 10.1016/j.jaut.2024.103205 |
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