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利用数学建模优化用于抗肿瘤放射治疗的纳米敏化剂的尺寸。

Optimization of Size of Nanosensitizers for Antitumor Radiotherapy Using Mathematical Modeling.

机构信息

P.N. Lebedev Physical Institute of the Russian Academy of Sciences, 53, Leninskiy Prospekt, Moscow 119991, Russia.

出版信息

Int J Mol Sci. 2023 Jul 22;24(14):11806. doi: 10.3390/ijms241411806.

Abstract

The efficacy of antitumor radiotherapy can be enhanced by utilizing nonradioactive nanoparticles that emit secondary radiation when activated by a primary beam. They consist of small volumes of a radiosensitizing substance embedded within a polymer layer, which is coated with tumor-specific antibodies. The efficiency of nanosensitizers relies on their successful delivery to the tumor, which depends on their size. Increasing their size leads to a higher concentration of active substance; however, it hinders the penetration of nanosensitizers through tumor capillaries, slows down their movement through the tissue, and accelerates their clearance. In this study, we present a mathematical model of tumor growth and radiotherapy with the use of intravenously administered tumor-specific nanosensitizers. Our findings indicate that their optimal size for achieving maximum tumor radiosensitization following a single injection of their fixed total volume depends on the permeability of the tumor capillaries. Considering physiologically plausible spectra of capillary pore radii, with a nanoparticle polymer layer width of 7 nm, the optimal radius of nanoparticles falls within the range of 13-17 nm. The upper value is attained when considering an extreme spectrum of capillary pores.

摘要

利用非放射性纳米粒子可以增强抗肿瘤放射治疗的效果,这些纳米粒子在被初级射束激活时会发射次级辐射。它们由嵌入聚合物层中的小体积放射增敏物质组成,聚合物层涂有肿瘤特异性抗体。纳米敏化剂的效率取决于它们成功递送到肿瘤的能力,这取决于它们的大小。增加它们的尺寸会导致更多的活性物质集中,但这会阻碍纳米敏化剂通过肿瘤毛细血管的渗透,减缓它们在组织中的移动速度,并加速它们的清除。在这项研究中,我们提出了一种利用静脉内给予肿瘤特异性纳米敏化剂进行肿瘤生长和放射治疗的数学模型。我们的研究结果表明,对于单次注射固定总体积的纳米敏化剂以实现最大肿瘤放射增敏作用,其最佳尺寸取决于肿瘤毛细血管的通透性。考虑到毛细血管孔径的生理上合理的范围,对于纳米粒子聚合物层宽度为 7nm,最佳纳米粒子半径在 13-17nm 范围内。当考虑毛细血管孔的极端范围时,会达到上限值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9659/10380738/6f0075444cf5/ijms-24-11806-g001.jpg

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