Sericin-based nanotherapeutics: A dual-action biological macromolecule for anti-urolithiatic and antibacterial applications.

Kidney stone (urolithiasis) is a prevalent global health issue with limited safe and cost-effective treatment options. This study investigates the anti-urolithiasis potential of sericin, a silk protein sustainably extracted from Bombyx mori cocoons, and its innovative nanoparticle formulations. Biocompatible sericin, sericin nanoparticles, and sericin coupled with a phytate chelator were developed and meticulously characterized. In in-vitro assays, sericin modified with phytate demonstrated the most potent antioxidant activity (IC50: 39.5 μg/mL) and the highest calcium oxalate stone inhibition (∼92 %, IC50: 30.1 μg/mL). It also exhibited significant antibacterial activity against E. coli, S. aureus, K. pneumoniae, and uropathogenic E. coli. In-vivo studies revealed improvements in urinary, blood, and serum parameters, reduced renal crystal size, and absence of tissue toxicity, as confirmed by histopathological analysis. This is the first report demonstrating sericin's efficacy in the prevention and treatment of urolithiasis in a rat model. Sericin nanoparticles, especially those crosslinked with phytate (PASS-NP), effectively crossed the compromised glomerular filtration barrier, localized in renal tubules, and disrupted calcium oxalate crystallization. The enhanced activity is attributed to the synergistic effects of sericin's antioxidant, anti-inflammatory, and antibacterial properties, and phytate's calcium-chelating and permeability-enhancing role. PASS-NP treatment showed significant crystal dissolution, reduced hematological disturbances, improved renal biomarkers, and strong antibacterial action against stone-promoting pathogens. These findings position sericin-based nanoparticles as multifunctional, biocompatible therapeutic agents offering a minimally invasive, eco-friendly, and cost-effective strategy for urolithiasis management potentially reducing drug load, recurrence, and healthcare costs.