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

Abstract

The level of collagen production critically determines skin wound contraction. If an intelligent skin drug delivery technology that enables the collagen production in a specific wound skin area is developed,...

Involvement of PAR-2 in the Induction of Cell-Specific Matrix Metalloproteinase-2 by Activated Protein C in Cutaneous Wound Healing

“…Unlike the consistent temporal expression of PAR-2 in skin cells [ 20 , 22 , 23 ], an important finding in the current work is that MMP-2 and -9 expression during wound healing was not only divergent among cell types but, importantly, altered over time. Consistently with the literature [ 45 ], our IHC showed that MMP-9 was primarily produced by the leading edge of the epithelial tongue and peaked at days 1 and 3.…”

“…Once activated, PAR-2 initiates a cascade of intracellular events leading to diverse cellular responses [ 10 , 36 , 38 ]. One prominent downstream effect of PAR-2 activation is the modulation of MMP expression, particularly MMP-2 and MMP-9 [ 23 , 24 ]. The relationship between PAR-2 and MMP-2 and -9 production has been established in various physiological and pathological contexts [ 10 , 39 ].…”

“…The relationship between PAR-2 and MMP-2 and -9 production has been established in various physiological and pathological contexts [ 10 , 39 ]. For instance, in tissue remodelling and wound healing, PAR-2 activation has been implicated in the regulation of MMP-2 and MMP-9, facilitating the controlled degradation of extracellular matrix proteins to enable cell migration and tissue repair [ 23 , 39 , 40 ]. Additionally, PAR-2-mediated MMP-2 and MMP-9 expression has been shown to be crucial in processes such as angiogenesis [ 41 ], where the remodelling of blood vessels requires the coordinated action of proteases [ 42 ].…”

“…We and others reported that human keratinocytes and dermal fibroblasts express PAR-2 [ 20 , 22 , 23 ]. Activation of PAR-2 stimulates the release of inflammatory mediators such as interleukin (IL)-6, IL-8, prostaglandin E2, matrix metalloproteinase (MMP)-2, and MMP-9, suggesting an important role of PAR-2 in inflammation and tissue remodelling [ 24 , 25 ].…”

Advances in active targeting of ligand-directed polymeric nanomicelles via exploiting overexpressed cellular receptors for precise nanomedicine

“…Lee and his co-workers developed a smart fibroblast targeting PMs via binding overexpressed PARs-2 for better wound healing performance. 144 Targeted PMs comprised amphiphilic PEO- b -PCL followed by functionalization with KTTKS; a collagen-derived peptide via thiol–maleimide conjugation technique 22 to form KTTKS/PEO- b -PCL nanomicelles. The inner core of the targeted micelles was loaded with CUR through hydrophobic interaction to give KTTKS/PEO- b -PCL-CUR nanomicelles.…”