Construction of Novel Polylysine/Sodium Alginate Nanocarriers Combining Chlorogenic Acid and siRNA against Keloids

Addressing the underappreciated critical role of angiogenesis and immune dysregulation in keloid formation, we developed a novel nanocarrier (PCS) based on a dual network of physical cross-linking for the efficient release of siTGF-β1 and chlorogenic acid. PCS was self-assembled from polyethylenimine/siTGF-β1 and chlorogenic acid-embedded polylysine/sodium alginate. The results demonstrated that PCS could inhibit the proliferation, induce apoptosis of human umbilical vein endothelial cells and human keloid fibroblasts by regulating their cell cycle, and improve the immune microenvironment at the lesion. By transcriptomics and network pharmacology analysis, PCS inhibited keloid development mainly through the TGF-β1/EGR1 signaling pathway. The final results of animal experiments also proved that the material exerted a favorable effect in keloid treatment. Overall, PCS, as a novel nanocarrier combining siRNA-based gene therapy with chlorogenic acid, was a promising approach for the treatment of keloids.