Fibroblast-targeting polymeric nanovehicles to enhance topical wound healing through promotion of PAR-2 receptor-mediated endocytosis

The level of collagen production critically determines skin wound contraction. If an intelligent skin drug delivery technology that enables collagen production in a specific wound skin area is developed, a breakthrough in wound healing treatment would be expected. However, such an intelligent drug delivery technology has not yet been developed as much as in the field of anticancer therapy. In this study, we propose a smart drug delivery system using polymeric nanovehicles (PNVs), in which the periphery is conjugated with a fibroblast-targeting collagen-derived peptide, KTTKS (Lys-Thr-Thr-Lys-Ser). We showed that surface engineering of PNVs with simultaneous PEGylation and peptide patching improved the dispersibility of PNVs, while promoting selective cellular uptake to fibroblasts via PAR-2 receptor-mediated endocytosis. In vitro collagen production and in vivo wound healing assays revealed that curcumin-loaded fibroblast-targeting PNVs significantly enhanced collagen production and wound healing activities, thus promising effective skin tissue regeneration.