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Theranostic combinatorial drug-loaded coated cubosomes for enhanced targeting and efficacy against cancer cells.
Cell Death & Disease ( IF 8.1 ) Pub Date : 2020-01-02 , DOI: 10.1038/s41419-019-2182-0 Leilei Zhang 1 , Jinlong Li 2 , Dan Tian 1 , Lihua Sun 1 , Xu Wang 1 , Miao Tian 3
Cell Death & Disease ( IF 8.1 ) Pub Date : 2020-01-02 , DOI: 10.1038/s41419-019-2182-0 Leilei Zhang 1 , Jinlong Li 2 , Dan Tian 1 , Lihua Sun 1 , Xu Wang 1 , Miao Tian 3
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Cubosomes, a product of nanobioengineering, are self-structured lipid nanoparticles that act like drug-loaded theranostic probes. Here, we describe a simple method for the preparation of combinatorial drug-loaded cubosomes with, proof-of-principle, therapeutic effect against cancer cells, along with diagnostic capabilities. Anticancer drugs cisplatin and paclitaxel were loaded in the cubosomes in combination. The cubosomes were coated with a layer of poly-Ɛ-lysine, which helped avoid the initial burst release of drug and allowed for a slow and sustained release for better efficacy. Cubosomes were imaged by transmission electron microscope, and their dispersion analyzed in vitro by differential scanning calorimetric and X-ray diffractogram studies. The microscopic images depicted spherical polyangular structures, which are easily distinguishable. The analyses revealed that the drug is uniformly dispersed all through the cubosomes. Further characterization was carried out by zeta-potential measurement, in vitro release, and entrapment efficiency studies. The in vitro studies established that the coating of cubosomes successfully reduced the burst release of drugs initially and confirmed a slow, sustained release over increased time. Comparative cytotoxicity of coated, uncoated, and blank cubosomes was evaluated, using human hepatoma HepG2 cell line, and the formulations were found to be entirely nontoxic, similar to the blank ones. The therapeutic efficiency of the cubosomes against HeLa cells was confirmed by the impedance measurement and fluorescent imaging. Furthermore, the reduction in impedance in cells treated with coated combinatorial cubosomes proved the impairment of HeLa cells, as confirmed by fluorescence microscopy.
中文翻译：
治疗诊断组合载药涂层立方体可增强针对癌细胞的靶向性和功效。
立方体是纳米生物工程的产物，是自结构的脂质纳米颗粒，其作用类似于载药治疗诊断探针。在这里，我们描述了一种制备组合载药立方体的简单方法，该方法具有原理证明、对癌细胞的治疗效果以及诊断能力。抗癌药物顺铂和紫杉醇被组合负载在立方体中。立方体上涂有一层聚赖氨酸，这有助于避免药物最初的突然释放，并允许缓慢而持续的释放以获得更好的疗效。通过透射电子显微镜对立方体进行成像，并通过差示扫描量热和 X 射线衍射图研究对其分散进行体外分析。显微图像描绘了易于区分的球形多角结构。分析表明，药物均匀地分散在整个立方体中。通过 zeta 电位测量、体外释放和包封效率研究进行了进一步表征。体外研究表明，立方体涂层最初成功地减少了药物的突发释放，并证实了随着时间的推移缓慢、持续的释放。使用人肝癌 HepG2 细胞系对包被、未包被和空白立方体的细胞毒性进行了比较，发现这些制剂完全无毒，与空白制剂类似。通过阻抗测量和荧光成像证实了立体体对 HeLa 细胞的治疗效率。此外，经荧光显微镜证实，用涂层组合立方体处理的细胞中阻抗的降低证明了 HeLa 细胞的损伤。
更新日期：2020-01-07
中文翻译：
治疗诊断组合载药涂层立方体可增强针对癌细胞的靶向性和功效。
立方体是纳米生物工程的产物，是自结构的脂质纳米颗粒，其作用类似于载药治疗诊断探针。在这里，我们描述了一种制备组合载药立方体的简单方法，该方法具有原理证明、对癌细胞的治疗效果以及诊断能力。抗癌药物顺铂和紫杉醇被组合负载在立方体中。立方体上涂有一层聚赖氨酸，这有助于避免药物最初的突然释放，并允许缓慢而持续的释放以获得更好的疗效。通过透射电子显微镜对立方体进行成像，并通过差示扫描量热和 X 射线衍射图研究对其分散进行体外分析。显微图像描绘了易于区分的球形多角结构。分析表明，药物均匀地分散在整个立方体中。通过 zeta 电位测量、体外释放和包封效率研究进行了进一步表征。体外研究表明，立方体涂层最初成功地减少了药物的突发释放，并证实了随着时间的推移缓慢、持续的释放。使用人肝癌 HepG2 细胞系对包被、未包被和空白立方体的细胞毒性进行了比较，发现这些制剂完全无毒，与空白制剂类似。通过阻抗测量和荧光成像证实了立体体对 HeLa 细胞的治疗效率。此外，经荧光显微镜证实，用涂层组合立方体处理的细胞中阻抗的降低证明了 HeLa 细胞的损伤。
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