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癌症纳米药物的计算建模:将热疗治疗整合到多相多孔介质肿瘤模型中。

Computational Modelling of Cancer Nanomedicine: Integrating Hyperthermia Treatment Into a Multiphase Porous-Media Tumour Model.

作者信息

Wirthl Barbara, Decuzzi Paolo, Schrefler Bernhard A, Wall Wolfgang A

机构信息

Institute for Computational Mechanics, Technical University of Munich, Garching, Germany.

Laboratory of Nanotechnology for Precision Medicine, Italian Institute of Technology, Genoa, Italy.

出版信息

Int J Numer Method Biomed Eng. 2025 Aug;41(8):e70074. doi: 10.1002/cnm.70074.

Abstract

Heat-based cancer treatment, so-called hyperthermia, can be used to destroy tumour cells directly or to make them more susceptible to chemotherapy or radiation therapy. To apply heat locally, iron oxide nanoparticles are injected into the bloodstream and accumulate at the tumour site, where they generate heat when exposed to an alternating magnetic field. However, the temperature must be precisely controlled to achieve therapeutic benefits while avoiding damage to healthy tissue. We therefore present a computational model for nanoparticle-mediated hyperthermia treatment fully integrated into a multiphase porous-media model of the tumour and its microenvironment. We study how the temperature depends on the amount of nanoparticles accumulated in the tumour area and the specific absorption rate of the nanoparticles. Our results show that host tissue surrounding the tumour is also exposed to considerable doses of heat due to the high thermal conductivity of the tissue, which may cause pain or even unnecessary irreversible damage. Further, we include a lumped and a discrete model for the cooling effect of blood perfusion. Using a discrete model of a realistic microvasculature reveals that the small capillaries do not have a significant cooling effect during hyperthermia treatment and that the commonly used lumped model based on Pennes' bioheat equation may overestimate the effect: within the specific conditions analysed, the difference between lumped and discrete approaches is approximatively 0.75°C, which could influence the therapeutic intervention outcome. Such a comprehensive computational model, as presented here, can provide insights into the optimal treatment parameters for nanoparticle-mediated hyperthermia and can be used to design more efficient treatment strategies.

摘要

基于热的癌症治疗,即所谓的热疗,可用于直接破坏肿瘤细胞或使它们对化疗或放射治疗更敏感。为了在局部施加热量,将氧化铁纳米颗粒注入血液中并在肿瘤部位聚集,在那里它们暴露于交变磁场时会产生热量。然而,必须精确控制温度以实现治疗效果,同时避免对健康组织造成损害。因此,我们提出了一种用于纳米颗粒介导的热疗的计算模型,该模型完全集成到肿瘤及其微环境的多相多孔介质模型中。我们研究温度如何取决于肿瘤区域中积累的纳米颗粒数量以及纳米颗粒的比吸收率。我们的结果表明,由于组织的高导热性,肿瘤周围的宿主组织也会受到相当剂量的热,这可能会引起疼痛甚至不必要的不可逆损伤。此外,我们纳入了一个集中模型和一个离散模型来描述血液灌注的冷却效果。使用逼真的微血管离散模型表明,在热疗过程中小毛细血管没有显著的冷却效果,并且基于佩恩斯生物热方程的常用集中模型可能会高估这种效果:在所分析的特定条件下,集中模型和离散模型之间的差异约为0.75°C,这可能会影响治疗干预结果。本文提出的这种全面的计算模型可以为纳米颗粒介导的热疗的最佳治疗参数提供见解,并可用于设计更有效的治疗策略。

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