Ultrasound-mediated oxygen nanotherapy as a potential therapeutic tool for hypoxia-related damage of superficial tissues.

Tissue hypoxia occurring in degenerative, ischemic or infectious diseases seriously undermines the processes of tissue repair associated with wound healing. For instance, it was previously shown that hypoxia strongly reduces secretion of human monocytic matrix metalloproteinase-9 (MMP-9), a proteolytic enzyme playing a crucial role in extracellular matrix turn-over. Thankfully, hypoxic regions are often located superficially; thus, topic administration of exogenous oxygen, encapsulated in suitable formulations of nanobubble solutions and provided through ultrasonic sonophoresis, might help to counteract hypoxia effects during wound healing. Oxygen-loaded nanobubbles (OLNs) are constituted by a shell of biocompatible material (dextran) and an oxygen-storing decafluoropentane (DFP) core, showing good capacity of oxygen delivery. In the present work the possible role of OLNs as therapeutical tools favouring tissue repair mechanisms during hypoxiaassociated diseases was evaluated by studying OLN sonophoresis throughout natural membranes and OLN effects on MMP-9 secretion from human monocytes in vitro. Results showed that US-activated OLNs trespassed significantly pig skin membranes increasing oxygen levels in the underlying compartment; on the other hand, OLNs abrogated hypoxia-dependent reduction of levels of human monocytic MMP-9. In conclusion, OLN sonication, being a non-invasive and low-cost nanotechnological device, appears to be a good candidate to treat hypoxia-related damage of superficial tissues.