光动力疗法在球体芯片模型上的治疗输出的计算模型。
Computational modelling of the therapeutic outputs of photodynamic therapy on spheroid-on-chip models.
发表日期:2024 Jul 04
作者:
Hossein Kazempour, Fatemeh Teymouri, Maryam Khatami, Seyed Nezamedin Hosseini
来源:
J Photoch Photobio B
摘要:
光动力疗法(PDT)是一种医学放射化疗方法,利用光、光敏剂和氧气产生细胞毒性化合物,消除恶性细胞。最近,微流体系统因其在体内环境中复制的潜力而被用于分析光敏剂(PS)。虽然先前的研究已经建立了反应单线态氧浓度与 PDT 诱导的细胞死亡之间的紧密相关性,但许多研究都忽略了环境流体流动可能对氧和 PS 浓度产生的影响,这限制了结果的可靠性。在此,我们将氧气和 PS 在整个环境介质和球状多细胞聚集体中的运输耦合起来,初步研究了辐射前后整个球体中氧和 PS 浓度以及 PDT 诱导的细胞死亡的分布。所得结果表明,PDT诱导的细胞死亡始于球体表面,随后扩散到邻近区域,这与实验结果非常吻合。随后,研究了药物光间隔 (DLI)、注量率、PS 组成、微通道高度和入口流速对治疗结果的影响。研究结果表明,足够的 DLI 对于确保 PS 在整个介质中均匀分布至关重要,并且发现 5 小时的值就足够了。 PS 的成分至关重要,因为 ALA-PpIX 会诱导细胞早期死亡,但会加速氧气消耗,尤其是在外层,剥夺内层 PDT 所需的氧气,与 mTHPC 和 Photofrin 相比,这反过来会破坏并延长曝光时间。尽管注量率直接影响单线态氧的生成速率,但将注量率增加 189 mW/cm2 不会给我们带来显着的好处。微孔高度和入口流速涉及竞争现象 - 增加高度或减少流量会减少氧气供应并增加 PS“冲洗”及其浓度。版权所有 © 2024。由 Elsevier B.V. 出版。
Photodynamic therapy (PDT) is a medical radio chemotherapeutic method that uses light, photosensitizing agents, and oxygen to produce cytotoxic compounds, which eliminate malignant cells. Recently, Microfluidic systems have been used to analyse photosensitizers (PSs) due to their potential to replicate in vivo environments. While prior studies have established a strong correlation between reacted singlet oxygen concentration and PDT-induced cellular death, the effects that the ambient fluid flow might have on the concentration of oxygen and PS have been disregarded in many, which limits the reliability of the results. Herein, we coupled the transport of oxygen and PS throughout the ambient medium and within the spheroidal multicellular aggregate to initially study the profiles of oxygen and PS concentration alongside PDT-induced cellular death throughout the spheroid before and after radiation. The attained results indicate that the PDT-induced cellular death initiates on the surface of the spheroids and subsequently spreads to the neighbouring regions, which is in great accordance with experimental results. Afterward, the effects that drug-light interval (DLI), fluence rate, PS composition, microchannel height, and inlet flow rate have on the therapeutic outcomes are studied. The findings show that adequate DLI is critical to ensure uniform distribution of PS throughout the medium, and a value of 5 h was found to be sufficient. The composition of PS is critical, as ALA-PpIX induces earlier cell death but accelerates oxygen consumption, especially in the outer layers, depriving the inner layers of oxygen necessary for PDT, which in turn disrupts and prolongs the exposure time compared to mTHPC and Photofrin. Despite the fluence rate directly influencing the singlet oxygen generation rate, increasing the fluence rate by 189 mW/cm2 would not significantly benefit us. Microwell height and inlet flow rate involve competing phenomena-increasing height or decreasing flow reduces oxygen supply and increases PS "washout" and its concentration.Copyright © 2024. Published by Elsevier B.V.