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Theranostic combinatorial drug-loaded coated cubosomes for enhanced targeting and efficacy against cancer cells.
Cell Death & Disease ( IF 9 ) 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
Affiliation  

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:

装载了治疗性组合药物的包衣立方小体,可增强靶向性和对癌细胞的功效。

纳米生物工程产品立方体是自结构的脂质纳米颗粒,其作用类似于载有药物的治疗药物探针。在这里,我们描述了一种简单的方法,用于制备组合药物负载的小体,其具有针对癌细胞的原理性证明,治疗作用以及诊断能力。将抗癌药顺铂和紫杉醇组合装入立方体中。立方脂质体被一层聚-γ-赖氨酸包被,这有助于避免药物的最初突释,并允许缓慢而持续的释放,以提高疗效。用透射电子显微镜对小体进行成像,并通过差示扫描量热法和X射线衍射图研究对它们的分散性进行体外分析。显微图像描绘了球形多角形结构,这是很容易区分的。分析表明,该药物均匀地分散在整个立方体中。通过ζ电位测量,体外释放和包封效率研究进行了进一步的表征。体外研究表明,立方脂质体包衣最初成功地减少了药物的爆发释放,并证实了随着时间的推移缓慢而持续的释放。使用人肝癌HepG2细胞系评估了包被的,未包被的和空白的立方体的比较细胞毒性,发现该制剂完全无毒,与空白的类似。通过阻抗测量和荧光成像证实了cubosomes对HeLa细胞的治疗效果。此外,经包被组合立方体处理的细胞的阻抗降低证明了HeLa细胞的损伤,
更新日期:2020-01-07
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