外来体是生物纳米囊泡,其固有地负载有数千个生物大分子,并且主要负责细胞与细胞之间的通信。受到自然有效载荷的启发,它们已被广泛调查为药物输送工具;然而,药物分布,无论是进入还是进入外泌体,仍然有争议。在目前的工作中,我们试图通过选择5-氟尿嘧啶(5-FU)(亲水性)和紫杉醇(PAC)(疏水性)来系统地研究它,具有非常不同的物理化学特性的药物,加载到外泌体。外泌体是从牛乳中获得的,使用三种不同的方法装载药物:孵育,超声处理,和tritonx-100.在所有情况下,发现粒径约为100nm;然而,在超声处理方法中发现最高的药物负载。荧光分光光度计,EDX分析,EDX映射,XPS,和XRD分析表明,在孵育方法的情况下,表面上可能存在更多的药物。通过超声处理方法加载的药物比简单的孵育和tritonx-100具有更多的受控释放。载药法对细胞毒性影响不明显,与我们之前的观察结果一致,通过ROS测定证明,组合(PAC和5-FU)表现出协同作用,集落形成试验,和线粒体膜电位测定。
Exosomes are biological nanovesicles that are intrinsically loaded with thousands of biomacromolecules and are principally responsible for cell-to-cell communication. Inspired by the natural payload, they have been extensively investigated as drug delivery vehicles; however, the drug distribution, whether into or onto exosomes, is still debatable. In the present work, we have tried to investigate it systemically by selecting 5-fluorouracil (5-FU) (hydrophilic) and paclitaxel (PAC) (hydrophobic), drugs with very different physicochemical characteristics, for the loading to the exosomes. Exosomes were obtained from bovine milk, and the drugs were loaded using three different methods: incubation, sonication, and triton x-100. The particle size was found to be approximately 100 nm in all the cases; however, the highest drug loading was found in the sonication method. Fluorescence spectrophotometer, EDX analysis, EDX mapping, XPS, and XRD analysis indicated the possible presence of more drugs over the surface in the case of the incubation method. Drugs loaded by the sonication method had more controlled release than simple incubation and triton x-100. The method of drug loading had an insignificant effect on the cytotoxicity while in line with our previous observation, the combination (PAC and 5-FU) exhibited synergism as evidenced by ROS assay, colony formation assay, and mitochondrial membrane potential assay.