Controlled Drug Release and Chemotherapy Response in a Novel Acoustofluidic 3D Tumor Platform.
Controlled Drug Release and Chemotherapy Response in a Novel Acoustofluidic 3D Tumor Platform.
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DOI：
10.1002/smll.201503342
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发表时间：
2016-05
期刊：
影响因子：
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通讯作者：
Arvanitis CD
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文献类型：
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作者：
Zervantonakis IK;Arvanitis CD
克服肿瘤治疗药物递送的运输障碍仍然是一个重大挑战。聚焦超声 (FUS) 与现代纳米医学药物配方相结合，能够最大限度地提高药物向肿瘤组织的转运，同时最大限度地降低对正常组织的毒性。由于目前准确评估和量化 FUS 如何调节实体瘤药物转运的方法存在局限性，这一潜力仍未得到实现。我们开发了一种新型声流控平台，将生理相关的 3D 微流控装置和带有闭环控制器的 FUS 系统集成在一起，以研究药物转运并使用活细胞显微镜实时评估癌细胞对化疗的反应。 FUS 诱导的加热触发了化疗药物阿霉素从脂质体载体的局部释放，并导致 FUS 焦点区域的细胞药物摄取更高。这种不同的药物摄取在 3D 环境中诱导局部限制性 DNA 损伤和胶质母细胞瘤细胞死亡。我们的研究证明了声流体在 3D 体外肿瘤模型中精确控制药物释放和监测局部细胞反应的能力，对于开发将治疗剂直接递送到肿瘤组织同时不伤害健康组织的新策略具有重要意义。一种新型 3D 声流控肿瘤平台，用于实时研究聚焦超声触发的药物释放对神经胶质瘤细胞系的影响，并监测肿瘤细胞死亡和 DNA 损伤。该平台可用于发现新的非侵入性方案，在不损害正常细胞的情况下局部靶向肿瘤细胞。
Overcoming transport barriers to delivery of therapeutic agents in tumors remains a major challenge. Focused ultrasound (FUS), in combination with modern nanomedicine drug formulations, offers the ability to maximize drug transport to tumor tissue while minimizing toxicity to normal tissue. This potential remains unfulfilled due to the limitations of current approaches in accurately assessing and quantifying how FUS modulates drug transport in solid tumors. We developed a novel acoustofluidic platform by integrating a physiologically relevant 3D microfluidic device and a FUS system with a closed-loop controller to study drug transport and assess the response of cancer cells to chemotherapy in real time using live cell microscopy. FUS-induced heating triggered local release of the chemotherapeutic agent doxorubicin from a liposomal carrier and resulted in higher cellular drug uptake in the FUS focal region. This differential drug uptake induced locally confined DNA damage and glioblastoma tumor cell death in the 3D environment. Our study demonstrates the capabilities of acoustofluidics for accurate control of drug release and monitoring of localized cell response in a 3D in vitro tumor model and has important implications for developing novel strategies to deliver therapeutic agents directly to the tumor tissue while sparing healthy tissue. A novel 3D acoustofluidic tumor platform to study the effects of focused ultrasound-triggered drug release in glioma cell lines in real time and monitor tumor cell death and DNA damage. This platform can be used to discover new non-invasive protocols that target tumor cells regionally without damaging normal cells.