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
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DOI：
10.1016/j.biomaterials.2023.122448
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发表时间：
2024-01-12
期刊：
影响因子：
14
通讯作者：
Stride，Eleanor
中科院分区：
文献类型：
--
作者：
Knowles，Helen J.;Vasilyeva，Alexandra;Stride，Eleanor
载气纳米气泡有潜力作为一种氧气输送方法，以增加肿瘤氧合和治疗缓解肿瘤缺氧。然而，载氧纳米气泡增加肿瘤氧合的机制尚不清楚;其计算的携氧能力不足以解释这种效应。肿瘤内缺氧是主要的治疗靶点，至少部分是由于缺氧依赖性刺激骨吸收破骨细胞的形成和功能，所述破骨细胞在骨中建立转移细胞。本研究旨在研究氧气输送的潜在机制，特别是载氧纳米气泡通过对破骨细胞的影响预防骨转移的可能用途。基于卵磷脂的纳米气泡优先与吞噬细胞（单核细胞，破骨细胞）通过脂质转移，网格蛋白依赖性内吞作用和吞噬作用的组合相互作用。这种相互作用通过抑制细胞融合引起破骨细胞分化的一般抑制。此外，重复暴露于载氧纳米气泡抑制破骨细胞形成的程度大于载氮纳米气泡。这种气体依赖性效应是由单核前体细胞融合形成前破骨细胞的差异效应驱动的，部分原因是载氮纳米气泡增强了RANKL诱导的ROS。我们的研究结果表明，载氧纳米气泡可以代表一种有前途的癌症治疗策略;除了直接改善肿瘤氧合的已知作用外，还可以通过与肿瘤和骨微环境中的单核细胞/巨噬细胞的优先相互作用来减少破骨细胞的形成，从而减少骨转移。
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.