The formation of polycrystalline aggregates in the glomerulus or other components of the urinary system is indisputably the most critical step in the formation of kidney stones and calcium oxalate monohydrate (CaCO·HO) is the most prevalent form. On the other hand, Annexin A1 (ANXA1), a calcium-binding protein, markedly increased on the apical surface of renal cells in CaCO-induced nephrolithiasis. In this regard, we identified the peptide motif responsible for calcium binding and redesigned it into a self-assembling peptide sequence without disturbing its binding selectivity for the CaCO interface. We developed a salt-dependent strategy to produce self-assembling spherical peptide nanoparticles by using aqueous solutions of R8 peptide and 16-amino acid designed peptide of net charge of -3 (WAEEFLKWLAFIEEFF). Peptide nanoparticles restored cell viability and reduced oxidative stress in MDCK cells triggered by CaCO crystals (80 µg cm) via Nrf2-HO-1 pathway activation. Peptide nanoparticles led to significant protection in urinary biochemistry and reducing calcifications without any toxicity.
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