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.

Polyphenol-modified nanovesicles for synergistically enhanced in vitro tumor cell targeting and apoptosis.

Tannic acid (TA) not only prevents drug carriers from sticking to the glycocalyx layer of vascular endothelial cells but also has anti-cancer properties, thereby improving drug delivery efficiency in cancer treatment. This study proposes a TANNylated nanovesicle-based cancer treatment approach by utilizing the aforementioned advantages of TA. We fabricated cancer cell-targeting BC71 peptide-conjugated TANNylated nanovesicles (TANVBC71) by covalently bonding the TA derivative and BC71 (cyclo[ßA-kRK(3-maleimidopropionyl)-D-(D-2-naphthyl)]) with thiol-modified phospholipids through the thiol-maleimide reaction. We demonstrated that TANVBC71 was absorbed faster in high amounts by cancer cells than nanovesicles owing to its high affinity for the epidermal growth factor receptor and extracellular matrix components that are driven by van der Waals attraction as well as hydrogen bonding and hydrophobic interactions in a complex manner. These complex attractions of TANVBC71 for cancer cells led to the effective induction of cancer cell apoptosis. The findings obtained in this study highlight that the TANVBC71 system has the potential for intelligent high-efficacy cancer cell drug delivery.