Metastasis causes the most breast cancer-related deaths in women. Here, we investigated the antitumor effect of solid lipid nanoparticles (SLN-DTX) when used in the treatment of metastatic breast tumors using 4T1-bearing BALB/c mice. Solid lipid nanoparticles (SLNs) were produced using the high-energy method. Compritol 888 ATO was selected as the lipid matrix, and Pluronic F127 and Span 80 as the surfactants to stabilize nanoparticle dispersion. The particles had high stability for at least 120 days. The SLNs’ dispersion size was 128 nm, their polydispersity index (PDI) was 0.2, and they showed a negative zeta potential. SLNs had high docetaxel (DTX) entrapment efficiency (86%), 2% of drug loading and showed a controlled drug-release profile. The half-maximal inhibitory concentration (IC50) of SLN-DTX against 4T1 cells was more than 100 times lower than that of free DTX after 24 h treatment. In the cellular uptake test, SLN-DTX was taken into the cells significantly more than free DTX. The accumulation in the G2-M phase was significantly higher in cells treated with SLN-DTX (73.7%) than in cells treated with free DTX (23.0%), which induced subsequent apoptosis. TEM analysis revealed that SLN-DTX internalization is mediated by endocytosis, and fluorescence microscopy showed DTX induced microtubule damage. In vivo studies showed that SLN-DTX compared to free docetaxel exhibited higher antitumor efficacy by reducing tumor volume (p < 0.0001) and also prevented spontaneous lung metastasis in 4T1 tumor-bearing mice. Histological studies of lungs confirmed that treatment with SLN-DTX was able to prevent tumor. IL-6 serum levels, ki-67 and BCL-2 expression were analyzed and showed a remarkably strong reduction when used in a combined treatment. These results indicate that DTX-loaded SLNs may be a promising carrier to treat breast cancer and in metastasis prevention.

中文翻译：

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装载多西他赛的固体脂质纳米颗粒可防止4T1鼠乳癌细胞的肿瘤生长和肺转移

转移导致女性与乳腺癌相关的死亡人数最多。在这里，我们研究了当使用携带4T1的BALB / c小鼠治疗转移性乳腺肿瘤时，固体脂质纳米颗粒（SLN-DTX）的抗肿瘤作用。使用高能方法生产了固态脂质纳米颗粒（SLN）。选择Compritol 888 ATO作为脂质基质，选择Pluronic F127和Span 80作为表面活性剂以稳定纳米颗粒的分散。颗粒具有至少120天的高稳定性。SLN的分散尺寸为128 nm，多分散指数（PDI）为0.2，并且显示负的Zeta电位。前哨淋巴结具有高的多西他赛（DTX）包封率（86​​％），2％的载药量，并显示出受控的药物释放曲线。处理24小时后，SLN-DTX对4T1细胞的半数最大抑制浓度（IC50）比游离DTX低100倍以上。在细胞摄取测试中，SLN-DTX被摄取到细胞中的数量明显多于游离DTX。用SLN-DTX处理的​​细胞（73.7％）在G2-M期的积累明显高于用游离DTX处理的​​细胞（23.0％），后者诱导随后的细胞凋亡。TEM分析显示SLN-DTX内在化是由内吞作用介导的，荧光显微镜检查显示DTX引起的微管损伤。体内研究表明，与游离多西他赛相比，SLN-DTX通过减少肿瘤体积（p <0.0001）表现出更高的抗肿瘤功效，并且还防止了4T1荷瘤小鼠的自发性肺转移。肺的组织学研究证实，SLN-DTX治疗能够预防肿瘤。分析了IL-6血清水平，ki-67和BCL-2表达，并在联合治疗中显示出明显的降低。这些结果表明，载有DTX的SLN可能是治疗乳腺癌和预防转移的有希望的载体。