ArticleJournal of nanobiotechnology2026
An oral nanocombinatorial agent exhibits pleiotropic improvement in diabetic nephropathy via modulation of the SCAP/SREBPs pathway.
Article in Journal of nanobiotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The multifaceted pathogenesis and multi-cellular involvement of diabetic nephropathy (DN) stand in stark contrast to the inadequacy of conventional single-target therapeutic strategies. This disparity underscores the urgent need for novel drugs with comprehensive targeting capabilities. Herein, the SREBP cleavage-activating protein/sterol regulatory element-binding proteins (SCAP/SREBPs) pathway was identified as a central driver in DN, where its activation in key renal parenchymal cells promotes lipid metabolic disorders and inflammation, thereby exacerbating renal injury. Guided by this discovery, we screened a 245-member nanoparticle library comprising SCAP inhibitors self-assembled with chitosan, and identified chitosan-lycorine nanoparticles (CLNPs) as the optimal candidate. Owing to its efficient intestinal absorption and significant accumulation in mesangial and proximal tubular epithelial cells, oral CLNPs strongly alleviated renal injury in a murine model of DN by counteracting lipid accumulation and inflammation, consistent with SCAP/SREBPs pathway inhibition. Critically, CLNPs prevented hepatotoxicity from free lycorine, which reduced mortality and enabled safer prolonged therapy. Together, our findings demonstrate the viability of CLNPs for DN, thereby offering a generalizable strategy for combating complex diseases through a single combinatorial agent that counters multiple co-existing pathological injuries.
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