Centro de Tecnología Biomédica (CTB), Campus de Montegancedo, Universidad Politécnica de Madrid (UPM), Pozuelo de Alarcón, 28223 Madrid, Spain.
CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28000 Madrid, Spain.
Int J Mol Sci. 2021 May 11;22(10):5091. doi: 10.3390/ijms22105091.
Although optical hyperthermia could be a promising anticancer therapy, the need for high concentrations of light-absorbing metal nanoparticles and high-intensity lasers, or large exposure times, could discourage its use due to the toxicity that they could imply. In this article, we explore a possible role of silica microparticles that have high biocompatibility and that scatter light, when used in combination with conventional nanoparticles, to reduce those high concentrations of particles and/or those intense laser beams, in order to improve the biocompatibility of the overall procedure. Our underlying hypothesis is that the scattering of light caused by the microparticles would increase the optical density of the irradiated volume due to the production of multiple reflections of the incident light: the nanoparticles present in the same volume would absorb more energy from the laser than without the presence of silica particles, resulting either in higher heat production or in the need for less laser power or absorbing particles for the same required temperature rise. Testing this new optical hyperthermia procedure, based on the use of a mixture of silica and metallic particles, we have measured cell mortality in vitro experiments with murine glioma (CT-2A) and mouse osteoblastic (MC3T3-E1) cell lines. We have used gold nanorods (GNRs) that absorb light with a wavelength of 808 nm, which are conventional in optical hyperthermia, and silica microparticles spheres (hereinafter referred to as SMSs) with a diameter size to scatter the light of this wavelength. The obtained results confirm our initial hypothesis, because a high mortality rate is achieved with reduced concentrations of GNR. We found a difference in mortality between CT2A cancer cells and cells considered non-cancer MC3T3, maintaining the same conditions, which gives indications that this technique possibly improves the efficiency in the cell survival. This might be related with differences in the proliferation rate. Since the experiments were carried out in the 2D dimensions of the Petri dishes, due to sedimentation of the silica particles at the bottom, whilst light scattering is a 3D phenomenon, a large amount of the energy provided by the laser escapes outside the medium. Therefore, better results might be expected when applying this methodology in tissues, which are 3D structures, where the multiple reflections of light we believe will produce higher optical density in comparison to the conventional case of no using scattering particles. Accordingly, further studies deserve to be carried out in this line of work in order to improve the optical hyperthermia technique.
尽管光热疗可能是一种很有前途的抗癌疗法,但由于其潜在的毒性,需要高浓度的光吸收金属纳米粒子和高强度激光,或者需要长时间的暴露,这可能会阻碍其应用。在本文中,我们探索了一种使用高生物相容性的二氧化硅微球的可能作用,当与传统纳米粒子结合使用时,可以减少这些高浓度的粒子和/或高强度的激光束,从而提高整个过程的生物相容性。我们的基本假设是,微球引起的光散射会由于入射光的多次反射而增加辐照体积的光密度:同一体积中存在的纳米粒子会比没有二氧化硅粒子时从激光中吸收更多的能量,从而导致更高的产热量,或者需要更少的激光功率或吸收粒子来达到相同的所需温升。通过测试基于使用混合二氧化硅和金属粒子的新型光热疗程序,我们已经在体外实验中测量了鼠胶质细胞瘤(CT-2A)和小鼠成骨细胞(MC3T3-E1)细胞系的细胞死亡率。我们使用了在光热疗中常规使用的吸收 808nm 波长光的金纳米棒(GNR)和散射该波长光的直径尺寸的二氧化硅微球(以下简称 SMS)。得到的结果证实了我们的初始假设,因为在降低 GNR 浓度的情况下,就可以实现高死亡率。我们发现 CT2A 癌细胞和被认为是非癌细胞 MC3T3 的细胞之间存在死亡率差异,在保持相同条件下,这表明该技术可能会提高细胞存活率的效率。这可能与增殖率的差异有关。由于实验是在培养皿的 2D 尺寸中进行的,由于二氧化硅颗粒在底部沉降,而光散射是 3D 现象,因此激光提供的大量能量会从介质中逸出。因此,当将这种方法应用于组织中时,可能会产生更好的结果,组织是 3D 结构,我们相信光的多次反射将产生比不使用散射粒子的情况下更高的光密度。因此,在这方面值得进一步开展研究工作,以改进光热疗技术。