Use of oxygen-loaded nanobubbles to improve tissue oxygenation: Bone-relevant mechanisms of action and effects on osteoclast differentiation

被引：4

作者：

Knowles, Helen J. ^{[1
]}

Vasilyeva, Alexandra ^{[1
,2
]}

Sheth, Mihir ^{[1
,2
]}

Pattinson, Oliver ^{[3
]}

May, Jonathan ^{[3
]}

Rumney, Robin M. H. ^{[4
]}

Hulley, Philippa A. ^{[1
]}

Richards, Duncan B. ^{[1
]}

Carugo, Dario ^{[1
]}

Evans, Nicholas D. ^{[3
]}

Stride, Eleanor ^{[1
,2
,5
]}

机构：

[1] Univ Oxford, Bot Inst Musculoskeletal Sci, Nuffield Dept Orthopaed Rheumatol & Musculoskeleta, Oxford, England

[2] Univ Oxford, Inst Biomed Engn, Dept Engn Sci, Oxford, England

[3] Univ Southampton, Southampton Gen Hosp, Bone & Joint Res Grp, Human Dev & Hlth,Fac Med, Southampton, England

[4] Univ Portsmouth, Sch Pharm & Biomed Sci, Portsmouth, England

[5] Univ Oxford, Bot Res Ctr, Nuffield Orthopaed Ctr, Oxford OX3 7LD, England

来源：

BIOMATERIALS | 2024年 / 305卷

基金：

英国工程与自然科学研究理事会;

关键词：

Nanobubble; Oxygen; Monocyte; Osteoclast; Osteoclastogenesis; Fusion; HYPOXIA; RESORPTION; DELIVERY;

D O I：

10.1016/j.biomaterials.2023.122448

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

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.

引用

页数：12