Abstract：
OBJECTIVE: The effectiveness of current microwave ablation (MWA) therapies is limited. Administration of thermosensitive liposomes (TSLs) which release drugs in response to heat has presented a significant potential for enhancing the efficacy of thermal ablation treatment, and the benefits of targeted drug delivery. However, a complete knowledge of the mechanobiological processes underlying the drug release process, especially the intravascular drug release mechanism and its distribution in response to MWA needs to be improved. Multiscale computational-based modeling frameworks, integrating different biophysical phenomena, have recently emerged as promising tools to decipher the mechanobiological events in combo therapies. The present study aims to develop a novel multiscale computational model of TSLs delivery following MWA implantation.
METHODS: Due to the complex interplay between the heating procedure and the drug concentration maps, a computational model is developed to determine the intravascular release of doxorubicin from TSL, its transvascular transport into the interstitium, transport in the interstitium, and cell uptake. Computational models can estimate the interplays among liposome and drug properties, tumor perfusion, and heating regimen to examine the impact of essential parameters and to optimize a targeted drug delivery platform.
RESULTS: Results indicated that the synergy of TSLs with MWA allows more localized drug delivery with lower side effects. The drug release rate and tumor permeability play crucial roles in the efficacy of TSLs during MWA treatment. The computational model predicted an unencapsulated drug lime around the ablated zone, which can destroy more cancer cells compared to MWA alone by 40%. Administration of TSLs with a high release rate capacity can improve the percentage of killed cancer cells by 24%. Since the heating duration in MWA is less than 15 min, the presented combination therapy showed better performance for highly permeable tumors.
CONCLUSIONS: This study highlights the potential of the proposed computational framework to address complex and realistic scenarios in cancer treatment, which can serve as the future research foundation, including advancements in nanomedicine and optimizing the pair of TSL and MWA for both preclinical and clinical studies. The present model could be as a valuable tool for patient-specific calibration of essential parameters.
METHODS: Due to the complex interplay between the heating procedure and the drug concentration maps, a computational model is developed to determine the intravascular release of doxorubicin from TSL, its transvascular transport into the interstitium, transport in the interstitium, and cell uptake. Computational models can estimate the interplays among liposome and drug properties, tumor perfusion, and heating regimen to examine the impact of essential parameters and to optimize a targeted drug delivery platform.
RESULTS: Results indicated that the synergy of TSLs with MWA allows more localized drug delivery with lower side effects. The drug release rate and tumor permeability play crucial roles in the efficacy of TSLs during MWA treatment. The computational model predicted an unencapsulated drug lime around the ablated zone, which can destroy more cancer cells compared to MWA alone by 40%. Administration of TSLs with a high release rate capacity can improve the percentage of killed cancer cells by 24%. Since the heating duration in MWA is less than 15 min, the presented combination therapy showed better performance for highly permeable tumors.
CONCLUSIONS: This study highlights the potential of the proposed computational framework to address complex and realistic scenarios in cancer treatment, which can serve as the future research foundation, including advancements in nanomedicine and optimizing the pair of TSL and MWA for both preclinical and clinical studies. The present model could be as a valuable tool for patient-specific calibration of essential parameters.
摘要：
目的：目前微波消融（MWA）治疗的有效性有限。热敏感脂质体（TSLs）的给药在热的反应中释放药物，在增强热消融治疗的功效方面具有重要的潜力。以及靶向药物递送的好处。然而,完全了解药物释放过程背后的机械生物学过程，特别是血管内药物释放机制及其响应MWA的分布有待改进。多尺度基于计算的建模框架，整合不同的生物物理现象，最近已成为破解组合疗法中机械生物学事件的有前途的工具。本研究旨在开发MWA植入后TSLs传递的新型多尺度计算模型。
方法：由于加热程序和药物浓度图之间复杂的相互作用，建立了一个计算模型来确定多柔比星从TSL的血管内释放，它的经血管转运到间质中，在间质中的运输，和细胞摄取。计算模型可以估计脂质体和药物性质之间的相互作用，肿瘤灌注，和加热方案，以检查基本参数的影响，并优化靶向药物递送平台。
结果：结果表明，TSL与MWA的协同作用允许更局部的药物递送，副作用更低。药物释放速率和肿瘤通透性在MWA治疗期间TSLs的疗效中起着至关重要的作用。计算模型预测了消融区周围的未包封药物石灰，与仅MWA相比，它可以破坏更多的癌细胞40％。施用具有高释放速率能力的TSLs可以将杀死的癌细胞的百分比提高24%。由于MWA中的加热持续时间小于15分钟，所提出的联合治疗对于高渗透性肿瘤显示出更好的表现.
结论：这项研究强调了拟议的计算框架在解决癌症治疗中复杂和现实场景方面的潜力。可以作为未来研究的基础，包括纳米医学的进步和优化TSL和MWA对的临床前和临床研究。本模型可以作为对基本参数的患者特异性校准的有价值的工具。
方法：由于加热程序和药物浓度图之间复杂的相互作用，建立了一个计算模型来确定多柔比星从TSL的血管内释放，它的经血管转运到间质中，在间质中的运输，和细胞摄取。计算模型可以估计脂质体和药物性质之间的相互作用，肿瘤灌注，和加热方案，以检查基本参数的影响，并优化靶向药物递送平台。
结果：结果表明，TSL与MWA的协同作用允许更局部的药物递送，副作用更低。药物释放速率和肿瘤通透性在MWA治疗期间TSLs的疗效中起着至关重要的作用。计算模型预测了消融区周围的未包封药物石灰，与仅MWA相比，它可以破坏更多的癌细胞40％。施用具有高释放速率能力的TSLs可以将杀死的癌细胞的百分比提高24%。由于MWA中的加热持续时间小于15分钟，所提出的联合治疗对于高渗透性肿瘤显示出更好的表现.
结论：这项研究强调了拟议的计算框架在解决癌症治疗中复杂和现实场景方面的潜力。可以作为未来研究的基础，包括纳米医学的进步和优化TSL和MWA对的临床前和临床研究。本模型可以作为对基本参数的患者特异性校准的有价值的工具。
