Hypoxia modifies the invasive phenotype of immune cells, thus playing a key role in several pathological conditions of different etiology, including chronic wounds, atherosclerosis and cancer. Intriguingly, such pathologies might be targeted by new effective oxygenating drugs such as O2-Loaded Nanobubbles (OLNs). In the present work, the effects of hypoxia on MMP/TIMP release from human adherent monocytes isolated from peripheral blood were investigated, and the therapeutic potential of dextran-shelled, decafluoropentane-containing OLNs was evaluated. Normoxic monocytes released basal MMP-9, TIMP-1 and TIMP-2 protein levels. Hypoxia strongly impaired MMP/TIMP balances by reducing MMP-9 and increasing TIMP-1, without affecting TIMP-2 secretion. Dextran OLNs, with spherical morphology, diameters of 550 nm and anionic surfaces, did not display cell cytotoxicity and did not affect cell viability of monocytes after uptake. Interestingly, OLNs abrogated all hypoxia effects, restoring normoxic MMP/TIMP levels. Such an event was specifically dependent on time-sustained O2 diffusion from OLN core, as it was mimicked by neither O2-saturated solution (OSS) nor O2-free nanobubbles (OFNs). In conclusion, dextran OLNs proved effective in counteracting hypoxia effects on MMP/TIMP balances in human monocytes, potentially presenting themselves as innovative, low-cost, non-toxic therapeutic devices which can restore physiological invasive phenotype of immune cells in hypoxia-associated diseases.

Dextran oxygen-loaded nanobubbles counteract hypoxia effects on MMP/TIMP balances in human adherent monocytes.

GULINO, GIULIA ROSSANA;KHADJAVI, AMINA;ARGENZIANO, MONICA;CAVALLI, Roberta;GIRIBALDI, Giuliana;GUIOT, Caterina;PRATO, Mauro
2013

Abstract

Hypoxia modifies the invasive phenotype of immune cells, thus playing a key role in several pathological conditions of different etiology, including chronic wounds, atherosclerosis and cancer. Intriguingly, such pathologies might be targeted by new effective oxygenating drugs such as O2-Loaded Nanobubbles (OLNs). In the present work, the effects of hypoxia on MMP/TIMP release from human adherent monocytes isolated from peripheral blood were investigated, and the therapeutic potential of dextran-shelled, decafluoropentane-containing OLNs was evaluated. Normoxic monocytes released basal MMP-9, TIMP-1 and TIMP-2 protein levels. Hypoxia strongly impaired MMP/TIMP balances by reducing MMP-9 and increasing TIMP-1, without affecting TIMP-2 secretion. Dextran OLNs, with spherical morphology, diameters of 550 nm and anionic surfaces, did not display cell cytotoxicity and did not affect cell viability of monocytes after uptake. Interestingly, OLNs abrogated all hypoxia effects, restoring normoxic MMP/TIMP levels. Such an event was specifically dependent on time-sustained O2 diffusion from OLN core, as it was mimicked by neither O2-saturated solution (OSS) nor O2-free nanobubbles (OFNs). In conclusion, dextran OLNs proved effective in counteracting hypoxia effects on MMP/TIMP balances in human monocytes, potentially presenting themselves as innovative, low-cost, non-toxic therapeutic devices which can restore physiological invasive phenotype of immune cells in hypoxia-associated diseases.
Get Connected!3– 3rd Wellcome Trust Centre for Cell-Matrix Research Conference 2013
Manchester, UK
11-13/09/2013
Get Connected!3– 3rd Wellcome Trust Centre for Cell-Matrix Research Conference 2013 - abstract book
Wellcome Trust Centre for Cell-Matrix Research
38
38
G.R. Gulino; C. Magnetto; A. Khadjavi; A. Panariti; M. Argenziano; I. Rivolta; A. Troia; R. Cavalli; G. Giribaldi; C. Guiot; M. Prato
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/138948
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact