Abstract

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@SiO₂) 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@SiO₂ 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.

中文翻译：

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使用甲氨蝶呤负载叶酸共轭 Au@SiO 2 纳米颗粒治疗乳腺癌的新型化疗光热疗法

 抽象的

低强度激光疗法（LLLT）被认为是一种针对肿瘤组织/细胞的安全光疗类型。此外，使用靶向纳米颗粒可以提高癌症治疗的成功率。本研究旨在研究叶酸 (FA)/甲氨蝶呤 (MTX) 负载二氧化硅包覆金 (Au@SiO ₂ ) 纳米颗粒 (NP) 和 LLLT 在对抗乳腺癌方面的综合作用。

使用 FTIR、TEM 和 DLS-Zeta 合成并表征了纳米颗粒。纳米粒子具有球形形态，平均直径约为 25 nm，带正电荷 (+13.3 mV)，而与 FA 和 MTX 缀合后，其净电荷减少至约 -19.7 mV。

我们的细胞摄取研究结果清楚地表明，由于叶酸受体的高表达，在两种乳腺癌细胞系中加载 FA 和 MTX 的 NP 后，细胞对 NP 的摄取增强，尤其是在 MDA-MB-231 上。结果表明，LLLT 对两种乳腺癌细胞系均具有增殖作用，但在工程化乳腺癌靶向纳米颗粒存在的情况下，使用 MTT 测定，联合化疗光热疗法的疗效显着增加 (p<0 id=13>2 NP LLLT 通过 DAPI 染色和细胞周期（通过增加 subG0/G1 中的细胞停滞）证明，化疗和 LLLT 的组合可以提高乳腺癌治疗的潜力，同时副作用最小。