Abstract：
Colon cancer (CC) is one of the most prevalent cancers in the world, and chemotherapy is widely applied to combat it. However, chemotherapy drugs have severe side effects and emergence of multi drug resistance (MDR) is common. This bottleneck can be overcome by niosome nanocarriers that minimize drug dose/toxicity meanwhile allow co-loading of incompatible drugs for combination therapy. In this research, silibinin (Sil) as a hydrophobic drug was loaded into the lipophilic part, and methotrexate (MTX) into the hydrophilic part of niosome by the thin film hydration (TFH) method to form Nio@MS NPs for CT26 colon cancer therapy in vitro. Our results indicated synthesis of ideal niosome nanoparticles (NPs) with spherical morphology, size of ~100 nm, and a zeta potential of -10 mV. The IC50 value for Nio@MS was determined ~2.6 µg/mL, which was significantly lower than MTX-Sil (~6.86 µg/mL), Sil (18.46 µg/mL), and MTX (9.8 µg/mL). Further, Nio@MS significantly reduced cell adhesion density, promoted apoptosis and increased gene expression level of caspase 3 and BAX while promoted significant downregulation of BCL2. In conclusion, the design and application of niosome to co-administer Sil and MTX can increase the drugs cytotoxicity, reduce their dose and improve anti-cancer potential by combating MDR.
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摘要：
结肠癌（CC）是世界上最常见的癌症之一，化疗被广泛应用于对抗它。然而,化疗药物副作用严重,多药耐药(MDR)的出现很常见。该瓶颈可以通过使药物剂量/毒性最小化同时允许联合治疗的不相容药物的共负载的脂质体纳米载体来克服。在这项研究中,水飞蓟宾（Sil）作为疏水性药物被加载到亲脂性部分，和甲氨蝶呤（MTX）通过薄膜水合（TFH）方法进入脂质体的亲水部分，形成Nio@MSNPs，用于CT26结肠癌的体外治疗。我们的结果表明合成了具有球形形态的理想的脂质体纳米颗粒（NPs），〜100nm的尺寸，和-10mV的ζ电位。Nio@MS的IC50值确定为〜2.6µg/mL，显着低于MTX-Sil（〜6.86µg/mL），Sil(18.46µg/mL),和MTX（9.8µg/mL）。Further,Nio@MS显著降低细胞粘附密度，促进细胞凋亡，增加caspase3和BAX的基因表达水平，同时促进BCL2的显著下调。总之,Sil和MTX共同给药的脂质体的设计和应用可以增加药物的细胞毒性，减少他们的剂量，并通过对抗MDR提高抗癌潜力。
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