Background: : In chronic wounds, efficient epithelial tissue repair is hampered by hypoxia, and balances between the molecules involved in matrix turn-over such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are seriously impaired. Intriguingly, new oxygenating nanocarriers such as 2H,3H-decafluoropentane-based oxygen-loaded nanodroplets (OLNs) might effectively target chronic wounds. Objective: : To investigate hypoxia and chitosan-shelled OLN effects on MMP/TIMP production by human keratinocytes. Methods: : HaCaT cells were treated for 24 h with 10% v/v OLNs both in normoxia or hypoxia. Cytotoxicity and cell viability were measured through biochemical assays; cellular uptake by confocal microscopy; and MMP and TIMP production by enzyme-linked immunosorbent assay or gelatin zymography. Results: : Normoxic HaCaT cells constitutively released MMP-2, MMP-9, TIMP-1 and TIMP-2. Hypoxia strongly impaired MMP/TIMP balances by reducing MMP-2, MMP-9, and TIMP-2, without affecting TIMP-1 release. After cellular uptake by keratinocytes, nontoxic OLNs abrogated all hypoxia effects on MMP/TIMP secretion, restoring physiological balances. OLN abilities were specifically dependent on time-sustained oxygen diffusion from OLN core. Conclusion: : Chitosan-shelled OLNs effectively counteract hypoxia-dependent dysregulation of MMP/TIMP balances in human keratinocytes. Therefore, topical administration of exogenous oxygen, properly encapsulated in nanodroplet formulations, might be a promising adjuvant approach to promote healing processes in hypoxic wounds.
Khadjavi, A., Magnetto, C., Panariti, A., Argenziano, M., Gulino, G., Rivolta, I., et al. (2015). Chitosan-shelled oxygen-loaded nanodroplets abrogate hypoxia dysregulation of human keratinocyte gelatinases and inhibitors: New insights for chronic wound healing. TOXICOLOGY AND APPLIED PHARMACOLOGY, 286(3), 198-206.
Citazione: | Khadjavi, A., Magnetto, C., Panariti, A., Argenziano, M., Gulino, G., Rivolta, I., et al. (2015). Chitosan-shelled oxygen-loaded nanodroplets abrogate hypoxia dysregulation of human keratinocyte gelatinases and inhibitors: New insights for chronic wound healing. TOXICOLOGY AND APPLIED PHARMACOLOGY, 286(3), 198-206. |
Tipo: | Articolo in rivista - Articolo scientifico |
Carattere della pubblicazione: | Scientifica |
Presenza di un coautore afferente ad Istituzioni straniere: | No |
Titolo: | Chitosan-shelled oxygen-loaded nanodroplets abrogate hypoxia dysregulation of human keratinocyte gelatinases and inhibitors: New insights for chronic wound healing |
Autori: | Khadjavi, A; Magnetto, C; Panariti, A; Argenziano, M; Gulino, G; Rivolta, I; Cavalli, R; Giribaldi, G; Guiot, C; Prato, M |
Autori: | |
Data di pubblicazione: | 2015 |
Lingua: | English |
Rivista: | TOXICOLOGY AND APPLIED PHARMACOLOGY |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/j.taap.2015.04.015 |
Appare nelle tipologie: | 01 - Articolo su rivista |