Use of oxygen-loaded nanobubbles to improve tissue oxygenation: bone-relevant mechanisms of action and effects on osteoclast differentiation
Use of oxygen-loaded nanobubbles to improve tissue oxygenation: bone-relevant mechanisms of action and effects on osteoclast differentiation
Gas-loaded nanobubbles have potential as a method of oxygen delivery to increase tumour oxygenation and therapeutically alleviate tumour hypoxia. However, the mechanism(s) whereby oxygen-loaded nanobubbles increase tumour oxygenation are unknown; with their calculated oxygen-carrying capacity being insufficient to explain this effect. Intra-tumoural hypoxia is a prime therapeutic target, at least partly due to hypoxia-dependent stimulation of the formation and function of bone-resorbing osteoclasts which establish metastatic cells in bone. This study aims to investigate potential mechanism(s) of oxygen delivery and in particular the possible use of oxygen-loaded nanobubbles in preventing bone metastasis via effects on osteoclasts. Lecithin-based nanobubbles preferentially interacted with phagocytic cells (monocytes, osteoclasts) via a combination of lipid transfer, clathrin-dependent endocytosis and phagocytosis. This interaction caused general suppression of osteoclast differentiation via inhibition of cell fusion. Additionally, repeat exposure to oxygen-loaded nanobubbles inhibited osteoclast formation to a greater extent than nitrogen-loaded nanobubbles. This gas-dependent effect was driven by differential effects on the fusion of mononuclear precursor cells to form pre-osteoclasts, partly due to elevated potentiation of RANKL-induced ROS by nitrogen-loaded nanobubbles. Our findings suggest that oxygen-loaded nanobubbles could represent a promising therapeutic strategy for cancer therapy; reducing osteoclast formation and therefore bone metastasis via preferential interaction with monocytes/macrophages within the tumour and bone microenvironment, in addition to known effects of directly improving tumour oxygenation.
Fusion, Monocyte, Nanobubble, Osteoclast, Osteoclastogenesis, Oxygen
Knowles, Helen J.
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Vasilyeva, Alexandra
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Sheth, Mihir
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Pattinson, Oliver
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May, Jonathan
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Rumney, Robin M.H.
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Hulley, Philippa A.
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Richards, Duncan B.
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Carugo, Dario
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Evans, Nicholas D.
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Stride, Eleanor
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12 January 2024
Knowles, Helen J.
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Vasilyeva, Alexandra
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Sheth, Mihir
efbfcab9-f758-449d-9d60-14a62ccdd79b
Pattinson, Oliver
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May, Jonathan
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Rumney, Robin M.H.
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Hulley, Philippa A.
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Richards, Duncan B.
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Carugo, Dario
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Evans, Nicholas D.
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Stride, Eleanor
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Knowles, Helen J., Vasilyeva, Alexandra, Sheth, Mihir, Pattinson, Oliver, May, Jonathan, Rumney, Robin M.H., Hulley, Philippa A., Richards, Duncan B., Carugo, Dario, Evans, Nicholas D. and Stride, Eleanor
(2024)
Use of oxygen-loaded nanobubbles to improve tissue oxygenation: bone-relevant mechanisms of action and effects on osteoclast differentiation.
Biomaterials, 305, [122448].
(doi:10.1016/j.biomaterials.2023.122448).
Abstract
Gas-loaded nanobubbles have potential as a method of oxygen delivery to increase tumour oxygenation and therapeutically alleviate tumour hypoxia. However, the mechanism(s) whereby oxygen-loaded nanobubbles increase tumour oxygenation are unknown; with their calculated oxygen-carrying capacity being insufficient to explain this effect. Intra-tumoural hypoxia is a prime therapeutic target, at least partly due to hypoxia-dependent stimulation of the formation and function of bone-resorbing osteoclasts which establish metastatic cells in bone. This study aims to investigate potential mechanism(s) of oxygen delivery and in particular the possible use of oxygen-loaded nanobubbles in preventing bone metastasis via effects on osteoclasts. Lecithin-based nanobubbles preferentially interacted with phagocytic cells (monocytes, osteoclasts) via a combination of lipid transfer, clathrin-dependent endocytosis and phagocytosis. This interaction caused general suppression of osteoclast differentiation via inhibition of cell fusion. Additionally, repeat exposure to oxygen-loaded nanobubbles inhibited osteoclast formation to a greater extent than nitrogen-loaded nanobubbles. This gas-dependent effect was driven by differential effects on the fusion of mononuclear precursor cells to form pre-osteoclasts, partly due to elevated potentiation of RANKL-induced ROS by nitrogen-loaded nanobubbles. Our findings suggest that oxygen-loaded nanobubbles could represent a promising therapeutic strategy for cancer therapy; reducing osteoclast formation and therefore bone metastasis via preferential interaction with monocytes/macrophages within the tumour and bone microenvironment, in addition to known effects of directly improving tumour oxygenation.
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Accepted/In Press date: 21 December 2023
e-pub ahead of print date: 28 December 2023
Published date: 12 January 2024
Keywords:
Fusion, Monocyte, Nanobubble, Osteoclast, Osteoclastogenesis, Oxygen
Identifiers
Local EPrints ID: 494120
URI: http://eprints.soton.ac.uk/id/eprint/494120
ISSN: 0142-9612
PURE UUID: dc0e37a9-8361-4c99-b793-be09833fd94c
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Date deposited: 24 Sep 2024 16:43
Last modified: 25 Sep 2024 01:42
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Contributors
Author:
Helen J. Knowles
Author:
Alexandra Vasilyeva
Author:
Mihir Sheth
Author:
Robin M.H. Rumney
Author:
Philippa A. Hulley
Author:
Duncan B. Richards
Author:
Dario Carugo
Author:
Eleanor Stride
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