An investigation into the cytotoxic effects of microbubbles and their constituents on osteosarcoma and bone marrow stromal cells.
An investigation into the cytotoxic effects of microbubbles and their constituents on osteosarcoma and bone marrow stromal cells.
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DOI：
10.1016/j.bbagen.2023.130481
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发表时间：
2023-10
期刊：
影响因子：
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通讯作者：
A. E. Polydorou;J. P. May;K. Makris;S. Ferri;Q. Wu;E. Stride;D. Carugo;N. D. Evans
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文献类型：
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作者：
A. E. Polydorou;J. P. May;K. Makris;S. Ferri;Q. Wu;E. Stride;D. Carugo;N. D. Evans
背景超声响应微泡提供了一种在包括再生医学在内的应用中实现微创、局部药物递送的手段。然而，为了促进其使用，重要的是要确定它们或其成分可能具有的任何细胞毒性作用。本研究的目的是测试磷脂壳微泡在生物相关浓度下对人骨源性细胞无毒的假设。方法使用1，2-二硬脂酰-sn-甘油-3-磷酸胆碱（DSPC）、1，2-二山酰-sn-甘油-3-磷酸胆碱（DBPC）、聚氧乙烯（40）硬脂酸酯（PEG 40 S）和1，2-二硬脂酰-sn-甘油基-3-磷酸乙醇胺-N-[甲氧基（聚乙二醇）-2000]（DSPE-PEG 2000）。通过光学显微镜测量作为时间和温度的函数的微泡尺寸和浓度。MG 63骨肉瘤和人骨髓基质细胞（BMSCs）的影响进行了测量长达72小时的测定活力，代谢活性和proliferation.ResultsDBPC：DSPE-PEG 2000微泡显着更稳定比DSPC：PEG 40 S微泡在所有条件下测试。含血清培养基对稳定性无不利影响，但与4 °C下相比，37 °C下储存降低了两种制剂的稳定性，在≥24 h时微泡几乎完全溶解。DSPC：PEG 40 S微泡对细胞代谢和生长的抑制作用强于DBPC：DSPE-PEG 2000微泡，其中PEG 40 S是主要的抑制成分。这些影响仅在高微泡浓度（≥20%（v/v））或长时间培养（≥24 h）时明显。增加细胞微泡接触倒置培养在一个定制的设备有没有抑制作用的metabolis.ConclusionsThese数据表明，在广泛的浓度和孵育时间，DBPC：DSPE-PEG 2000和DSPC：PEG 40 S微泡对成骨细胞的活力和生长的影响不大，和PEG 40 S是主要的抑制成分的配方研究。
BackgroundUltrasound-responsive microbubbles offer a means of achieving minimally invasive, localised drug delivery in applications including regenerative medicine. To facilitate their use, however, it is important to determine any cytotoxic effects they or their constituents may have. The aim of this study was to test the hypothesis that phospholipid-shelled microbubbles are non-toxic to human bone-derived cells at biologically-relevant concentrations.MethodsMicrobubbles were fabricated using combinations of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dibehenoyl-sn-glycero-3-phosphocholine (DBPC), polyoxyethylene(40) stearate (PEG40S) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene-glycol)-2000] (DSPE-PEG2000). Microbubble size and concentration were measured as a function of time and temperature by optical microscopy. Effects on MG63 osteosarcoma and human bone marrow stromal cells (BMSCs) were measured for up to 72 h by assay for viability, metabolic activity and proliferation.ResultsDBPC:DSPE-PEG2000microbubbles were significantly more stable than DSPC:PEG40S microbubbles under all conditions tested. Serum-containing medium had no detrimental effect on stability, but storage at 37 °C compared to at 4 °C reduced stability for both preparations, with almost complete dissolution of microbubbles at times ≥24 h. DSPC:PEG40S microbubbles had greater inhibitory effects on cell metabolism and growth than DBPC:DSPE-PEG2000microbubbles, with PEG40S found to be the principle inhibitory component. These effects were only evident at high microbubble concentration (≥20% (v/v)) or with prolonged culture (≥24 h). Increasing cell-microbubble contact by inversion culture in a custom-built device had no inhibitory effect on metabolism.ConclusionsThese data indicate that, over a broad range of concentrations and incubation times, DBPC:DSPE-PEG2000and DSPC:PEG40S microbubbles have little effect on osteoblastic cell viability and growth, and that PEG40S is the principle inhibitory component in the formulations investigated.