Department of Oncology, The First People's Hospital of Jingmen, Jingmen, Hubei 448000, China.
Department of Clinical Laboratory, The Second People's Hospital of Jingmen, Jingmen, Hubei 448000, China.
Colloids Surf B Biointerfaces. 2017 Nov 1;159:880-887. doi: 10.1016/j.colsurfb.2017.08.042. Epub 2017 Aug 30.
In this study, paclitaxel and etoposide-loaded lipid-polymer hybrid nanoparticles (PE-LPN) was successful prepared and evaluated for physicochemical and anticancer effect. Nanosized PE-LPN was obtained with a perfect spherical morphology. PE-LPN exhibited a controlled release of two drugs in a sequential manner. The nanoparticles exhibited a typical endocytosis-mediated cellular uptake in cancer cells. The ratiometric combination of paclitaxel (PTX) and etoposide (ETP) were significantly more cytotoxic than individual drugs. Importantly, superior cytotoxic effect was observed for dual-drug-loaded PE-LPN than cocktail combination at a much lower dose. Similarly, PE-LPN exhibited a significantly higher apoptosis of cancer cells (∼45%) compared to that of any other groups with higher caspase-3 and -8 activity. Importantly, PE-LPN showed a remarkable tumor regression effect and exhibited a 2-fold superior efficacy than free drugs. PE-LPN treated group showed significantly less Ki-67 positive cells (less than 25%) than PTX/ETP and single drug treated groups, suggesting less active cell proliferation and a considerably higher tumor growth inhibition effect. The results collectively showed that combination of drugs could greatly improve the therapeutic property of chemotherapeutic drugs. By combining ETP with PTX (a powerful anticancer drug) in a polymer-lipid hybrid nanoparticle system, therapeutic efficacy could be improved in osteosarcoma treatments.
在这项研究中，成功制备并评价了载紫杉醇和依托泊苷的脂质-聚合物杂化纳米粒（PE-LPN）的理化性质和抗癌效果。得到了具有完美球形形态的纳米级 PE-LPN。PE-LPN 以顺序方式表现出两种药物的控制释放。纳米粒在癌细胞中表现出典型的内吞作用介导的细胞摄取。紫杉醇（PTX）和依托泊苷（ETP）的比例组合比单独使用两种药物具有更高的细胞毒性。重要的是，与鸡尾酒组合相比，双载药 PE-LPN 在低得多的剂量下显示出更好的细胞毒性作用。同样，与其他任何组相比，PE-LPN 表现出更高的癌细胞凋亡（约 45%），同时具有更高的 caspase-3 和 -8 活性。重要的是，PE-LPN 显示出显著的肿瘤消退作用，疗效比游离药物高 2 倍。PE-LPN 治疗组的 Ki-67 阳性细胞（少于 25%）明显少于 PTX/ETP 和单药治疗组，表明细胞增殖活性较低，肿瘤生长抑制作用较高。结果表明，联合用药可显著改善化疗药物的治疗特性。通过将 ETP 与 PTX（一种有效的抗癌药物）结合在聚合物-脂质杂化纳米粒系统中，可以提高骨肉瘤治疗的疗效。
