Research Article Oxygen-Loaded Nanodroplets Effectively Abrogate Hypoxia Dysregulating Effects on Secretion of MMP-9 and TIMP-1 by Human Monocytes Giulia Rossana Gulino, 1 Chiara Magnetto, 2 Amina Khadjavi, 3 Alice Panariti, 4 Ilaria Rivolta, 4 Marco Soster, 5 Monica Argenziano, 5 Roberta Cavalli, 5 Giuliana Giribaldi, 1 Caterina Guiot, 3 and Mauro Prato 3,6 1 Dipartimento di Oncologia, Universit` a di Torino, 10126 Torino, Italy 2 Istituto Nazionale di Ricerca Metrologica (INRIM), 10135 Torino, Italy 3 Dipartimento di Neuroscienze, Universit` a di Torino, 10125 Torino, Italy 4 Dipartimento di Scienze della Salute, Universit` a di Milano Bicocca, 20900 Monza, Italy 5 Dipartimento di Scienza e Tecnologia del Farmaco, Universit` a di Torino, 10125 Torino, Italy 6 Dipartimento di Scienze della Sanit` a Pubblica e Pediatriche, Universit` a di Torino, 10126 Torino, Italy Correspondence should be addressed to Mauro Prato; mauro.prato@unito.it Received 12 January 2015; Accepted 9 March 2015 Academic Editor: Elzbieta Kolaczkowska Copyright © 2015 Giulia Rossana Gulino et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Monocytes play a key role in the inlammatory stage of the healing process. To allow monocyte migration to injured tissues, the balances between secreted matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) must be inely modulated. However, a reduction of blood supply and local oxygen tension can modify the phenotype of immune cells. Intriguingly, hypoxia might be targeted by new efective oxygenating devices such as 2H,3H-decaluoropentane- (DFP-) based oxygen-loaded nanodroplets (OLNs). Here, hypoxia efects on gelatinase/TIMP release from human peripheral monocytes were investigated, and the therapeutic potential of dextran-shelled OLNs was evaluated. Normoxic monocytes constitutively released ∼500 ng/mL MMP-9, ∼1.3 ng/mL TIMP-1, and ∼0.6 ng/mL TIMP-2 proteins. MMP-2 was not detected. Ater 24 hours, hypoxia signiicantly altered MMP-9/TIMP-1 balance by reducing MMP-9 and increasing TIMP-1, without afecting TIMP-2 secretion. Interestingly OLNs, not displaying toxicity to human monocytes ater cell internalization, efectively counteracted hypoxia, restoring a normoxia-like MMP-9/TIMP-1 ratio. he action of OLNs was speciically dependent on time-sustained oxygen difusion up to 24 h from their DFP-based core. herefore, OLNs appear as innovative, nonconventional, cost-efective, and nontoxic therapeutic tools, to be potentially employed to restore the physiological invasive phenotype of immune cells in hypoxia-associated inlammation. 1. Introduction he innate immune system provides the irst line of defense against exogenous or endogenous danger signals, promoting a protective inlammatory response that evolves through diferent phases, from initiation and full inlammation to resolution and reestablishment of tissue integrity. In this perspective, inlammation has been described as an adaptive response to tissue malfunction or homeostatic imbalance [1]. However, the inlammatory activities are potentially harmful to the host; therefore, they need to be tightly controlled to prevent excessive tissue damage [2]. Human monocytes, constituting almost 10% of the total leukocytes, play a central role in the diferent stages of the inlammatory response, including antigen recognition and presentation, initiation of the adaptive immune response, and regulation of healing Hindawi Publishing Corporation Mediators of Inflammation Volume 2015, Article ID 964838, 11 pages http://dx.doi.org/10.1155/2015/964838