实体瘤中间质-淋巴液流动与纳米药物传输的有限元模拟:瘤内注射方法

Finite Element Simulation of Interstitial-Lymphatic Fluid Flow and Nanodrug Transport in a Solid Tumor: An Intratumoral Injection Approach.

作者信息

Debnath Gobinda, Vasu Buddakkagari, Gorla Rama Subba Reddy

机构信息

Department of Mathematics, Motilal Nehru National Institute of Technology Allahabad, Prayagraj 211004, UP, India.

Department of Aeronautics and Astronautics, Air Force Institute of Technology, Wright Patterson Air Force Base, Dayton, OH 45433, USA.

出版信息

BME Front. 2025 Jun 6;6:0119. doi: 10.34133/bmef.0119. eCollection 2025.

Abstract

This study presents a mathematical model and finite element simulations to investigate interstitial fluid flow and nanodrug transport in a solid tumor, incorporating transvascular exchange, convection-diffusion-reaction dynamics, and intratumoral injection mechanisms. Optimizing nanodrug distribution remains a critical challenge in cancer therapy. The proposed model advances nanomedicine by enhancing the mechanistic understanding of nanodrug transport in a solid tumor. Cancer, a global threat, often manifests as solid tumors driven by uncontrolled cell growth. The heterogeneous microenvironment, lymphatic drainage, nano-bio interactions, and elevated interstitial fluid pressure (IFP) hinder effective nanodrug delivery. Nanoparticle (NP)-based drug delivery systems offer a promising solution, with FES providing an effective approach to model and simulate the complex delivery process. The model considered a spherical and symmetrical tumor architecture comprising a central necrosis region, viable tumor, and surrounding healthy tissue with functional lymphatic dynamics. Substantial nanodrug carriers (dextran, liposomal, polyethylene glycol (PEG)-coated gold, and magnetic) and conventional doxorubicin are evaluated in the tumor. The governing fluid flow and solute transport equation along with the specified boundary conditions are solved using the finite element method through the Galerkin approach. Simulations show that IFP peaks in the necrotic core and sharply declines at the viable-healthy tissue interface. Both fluid pressure and velocity are sensitive when fluid flow resistance drops below 5. Necrotic core size influences IFP, and critical necrotic radius ( ) marks pressure stabilization and defines the threshold for effective nanodrug delivery. Vascular normalization and functional lymphatic dynamics show marginal impact. Smaller NPs (~10 nm) diffuse faster but undergo rapid degradation, while larger particles (>30 nm) exhibit prolonged retention at the injection site. Liposomal, PEG-coated gold, and magnetic variants demonstrate superior therapeutic action compared to conventional doxorubicin. The findings of the study highlight its strong potential for optimizing nanodrug delivery and design, as well as hyperthermia treatment, enhancing personalized cancer therapy.

摘要

本研究提出了一个数学模型和有限元模拟,以研究实体肿瘤中的间质液流动和纳米药物传输,纳入了跨血管交换、对流-扩散-反应动力学以及瘤内注射机制。优化纳米药物分布仍然是癌症治疗中的一项关键挑战。所提出的模型通过增强对实体肿瘤中纳米药物传输的机理理解,推动了纳米医学的发展。癌症是一种全球性威胁,通常表现为由不受控制的细胞生长驱动的实体肿瘤。异质性微环境、淋巴引流、纳米-生物相互作用以及升高的间质液压力(IFP)阻碍了有效的纳米药物递送。基于纳米颗粒(NP)的药物递送系统提供了一个有前景的解决方案,有限元模拟(FES)为模拟和仿真复杂的递送过程提供了一种有效方法。该模型考虑了一个球形且对称的肿瘤结构,包括中央坏死区域、存活肿瘤以及具有功能性淋巴动力学的周围健康组织。在肿瘤中评估了大量的纳米药物载体(葡聚糖、脂质体、聚乙二醇(PEG)包被的金以及磁性载体)和传统的阿霉素。通过伽辽金方法使用有限元法求解控制流体流动和溶质传输的方程以及指定的边界条件。模拟结果表明,IFP在坏死核心处达到峰值,并在存活-健康组织界面处急剧下降。当流体流动阻力降至5以下时,流体压力和速度都很敏感。坏死核心大小影响IFP,临界坏死半径( )标志着压力稳定,并定义了有效纳米药物递送的阈值。血管正常化和功能性淋巴动力学显示出边际影响。较小的纳米颗粒(约10纳米)扩散更快,但会迅速降解,而较大的颗粒(>30纳米)在注射部位表现出较长的滞留时间。与传统阿霉素相比,脂质体、PEG包被的金和磁性变体表现出更好的治疗效果。该研究结果突出了其在优化纳米药物递送和设计以及热疗方面的强大潜力,增强了个性化癌症治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af71/12143167/8cc15d9470e6/bmef.0119.fig.001.jpg

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