Chemical Engineering Department, Bioengineering Division and Bioengineering Centre, Hacettepe University, Ankara 06800, Turkey.
Chemical Engineering and Applied Chemistry Department, Atilim University, Ankara 06830, Turkey.
Int J Nanomedicine. 2020 Apr 24;15:2903-2920. doi: 10.2147/IJN.S248327. eCollection 2020.
The development of highly efficient nanoparticles to convert light to heat for anti-cancer applications is quite a challenging field of research.
In this study, we synthesized unique pimpled gold nanospheres (PGNSs) for plasmonic photothermal therapy (PPTT). The light-to-heat conversion capability of PGNSs and PPTT damage at the cellular level were investigated using a tissue phantom model. The ability of PGNSs to induce robust cellular damage was studied during cytotoxicity tests on colorectal adenocarcinoma (DLD-1) and fibroblast cell lines. Further, a numerical model of plasmonic (COMSOL Multiphysics) properties was used with the PPTT experimental assays.
A low cytotoxic effect of thiolated polyethylene glycol (SH-PEG-SH-) was observed which improved the biocompatibility of PGNSs to maintain 89.4% cell viability during cytometry assays (in terms of fibroblast cells for 24 hrs at a concentration of 300 µg/mL). The heat generated from the nanoparticle-mediated phantom models resulted in ΔT=30°C, ΔT=23.1°C and ΔT=21°C for the PGNSs, AuNRs, and AuNPs, respectively (at a 300 µg/mL concentration and for 325 sec). For the in vitro assays of PPTT on cancer cells, the PGNS group induced a 68.78% lethality (apoptosis) on DLD-1 cells. Fluorescence microscopy results showed the destruction of cell membranes and nuclei for the PPTT group. Experiments further revealed a penetration depth of sufficient PPTT damage in a physical tumor model after hematoxylin and eosin (H&E) staining through pathological studies (at depths of 2, 3 and 4 cm). Severe structural damages were observed in the tissue model through an 808-nm laser exposed to the PGNSs.
Collectively, such results show much promise for the use of the present PGNSs and photothermal therapy for numerous anti-cancer applications.
开发高效的纳米粒子将光转化为热量用于癌症治疗是一个极具挑战性的研究领域。
在这项研究中,我们合成了独特的凹凸不平的金纳米球(PGNSs)用于光热治疗(PPTT)。使用组织模型研究了 PGNSs 的光热转换能力和细胞水平的 PPTT 损伤。在对结直肠癌细胞(DLD-1)和成纤维细胞系进行细胞毒性试验时,研究了 PGNSs 诱导强烈细胞损伤的能力。此外,还使用等离子体(COMSOL Multiphysics)特性的数值模型与 PPTT 实验进行了比较。
巯基化聚乙二醇(SH-PEG-SH-)的低细胞毒性作用提高了 PGNSs 的生物相容性,使其在细胞计数测定中保持 89.4%的细胞活力(在 300μg/mL 浓度下,24 小时内的成纤维细胞)。在纳米粒子介导的模型中产生的热量导致 PGNSs、AuNRs 和 AuNPs 的 ΔT 分别为 30°C、ΔT=23.1°C 和 ΔT=21°C(在 300μg/mL 浓度和 325 秒)。在体外 PPTT 对癌细胞的测定中,PGNS 组诱导 DLD-1 细胞的 68.78%的致死率(凋亡)。荧光显微镜结果显示,PGNS 组的细胞膜和细胞核破裂。实验还进一步通过组织学研究(在 2、3 和 4 cm 深度)显示,在物理肿瘤模型中,使用 808nm 激光照射 PGNS 后,具有足够深度的 PPTT 损伤。在组织模型中观察到严重的结构损伤。
总的来说,这些结果为使用本研究中的 PGNSs 和光热疗法进行多种癌症治疗提供了很大的希望。