Agabeigi Reza, Rasta Seyed Hossein, Rahmati-Yamchi Mohammad, Salehi Roya, Alizadeh Effat
Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Medical Bioengineering, Tabriz University of Medical Sciences, Tabriz, Iran.
Nanoscale Res Lett. 2020 Mar 19;15(1):62. doi: 10.1186/s11671-020-3295-1.
Low level laser therapy (LLLT) is known as a safe type of phototherapy to target tumor tissue/cells. Besides, using targeted nanoparticles increases the successfulness of cancer therapy. This study was designed for investigating the combined effect of folate (FA)/Methotrexate (MTX) loaded silica coated gold (Au@SiO) nanoparticles (NPs) and LLLT on the fight against breast cancer.NPs were synthesized and characterized using FTIR, TEM and DLS-Zeta. The NPs had spherical morphology with mean diameter of around 25 nm and positive charge (+13.3 mV) while after conjugation with FA and MTX their net charge reduced to around -19.7 mV.Our findings in cell uptake studies clearly showed enhanced cellular uptake of NPs after FA and MTX loaded NPs in both breast cancer cell lines especially on MDA-MB-231 due to high expression of folate receptors. The results indicated that LLLT had a proliferative effect on both breast cancer cell lines but in the presence of engineered breast cancer targeted nanoparticle, the efficacy of combination chemo-photothermal therapy was significantly increased using MTT assay (p<0.05), DAPI staining, and cell cycle findings. The highest apoptotic effect on breast cancer cell lines was observed in the cells exposed to a combination of MTX-FA loaded Au@SiO NP and LLLT proved by DAPI staining and cell cycle(by increasing the cell arrest in subG0/G1). Taken together a combination of chemotherapy and LLLT improves the potential of breast cancer therapy with minimum side effects.
低强度激光疗法（LLLT）是一种已知的针对肿瘤组织/细胞的安全光疗类型。此外，使用靶向纳米颗粒可提高癌症治疗的成功率。本研究旨在调查负载叶酸（FA）/甲氨蝶呤（MTX）的二氧化硅包覆金（Au@SiO）纳米颗粒（NPs）与LLLT联合对抗乳腺癌的效果。使用傅里叶变换红外光谱（FTIR）、透射电子显微镜（TEM）和动态光散射-ζ电位（DLS-Zeta）对NPs进行合成和表征。这些NPs呈球形形态，平均直径约为25 nm，带正电荷（+13.3 mV），而与FA和MTX共轭后，其净电荷降至约-19.7 mV。我们在细胞摄取研究中的发现清楚地表明，在两种乳腺癌细胞系中，尤其是在MDA-MB-231细胞系中，由于叶酸受体的高表达，负载FA和MTX的NPs后细胞对NPs的摄取增强。结果表明，LLLT对两种乳腺癌细胞系均有增殖作用，但在工程化的乳腺癌靶向纳米颗粒存在的情况下，使用MTT法（p<0.05）、4',6-二脒基-2-苯基吲哚（DAPI）染色和细胞周期研究结果显示，联合化学-光热疗法的疗效显著提高。通过DAPI染色和细胞周期（通过增加细胞在亚G0/G1期的停滞）证明，在暴露于负载MTX-FA的Au@SiO NP和LLLT组合的细胞中观察到对乳腺癌细胞系的最高凋亡作用。综上所述，化疗和LLLT的联合使用可提高乳腺癌治疗的潜力，且副作用最小。
