Faculty of Biotechnology, October University for Modern Sciences and Arts, 6th of October City, Giza, Egypt.
Pharmacognosy Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Giza, Egypt.
Sci Rep. 2024 May 14;14(1):10964. doi: 10.1038/s41598-024-59736-7.
Due to vincristine sulfate's (VCR sulfate) toxicity and non-specific targeting, which might adversely damage healthy cells, its clinical application is restricted. In this study, we loaded VCR sulfate on exosomes generated from mesenchymal stem cells (MSCs) to enhance its targeted distribution. Exosomes are able to deliver molecules to specific cells and tissues and have therapeutic potential. In this study, we isolated exosomes from MSCs, and using probe-sonication approach loaded them with VCR sulfate. Using SRB assay, the cytotoxicity of VCR sulfate-Exo was assessed in T47D breast cancer cells, and the results were contrasted with those of free VCR sulfate. Then We labeled markers (CD44+/CD24-) in the cell line to assess the targeting effectiveness of VCR sulfate-Exo using flow cytometry. Our results showed that the cytotoxicity of VCR sulfate-Exo was nearly the same as that of VCR sulfate. Flow cytometry analysis revealed that VRC sulfate-Exo was more effectively targeted to MSCs than free VCR sulfate. Our study shows that loading VCR sulfate to MSCs-derived exosomes can improve their targeted delivery and lessen their side effects. Additional research is required to determine VCR sulfate-Exo's in vivo effectiveness and safety and improve the loading and delivery strategies.
由于硫酸长春新碱(VCR 硫酸盐)的毒性和非特异性靶向性,可能会对健康细胞造成不良损害,其临床应用受到限制。在本研究中,我们将 VCR 硫酸盐加载到间充质干细胞(MSCs)产生的外泌体中,以增强其靶向分布。外泌体能够将分子递送到特定的细胞和组织,并具有治疗潜力。在本研究中,我们从 MSCs 中分离出外泌体,并使用探针超声方法将其加载 VCR 硫酸盐。使用 SRB 测定法,在 T47D 乳腺癌细胞中评估 VCR 硫酸盐-Exo 的细胞毒性,并将结果与游离 VCR 硫酸盐进行对比。然后,我们标记细胞系中的标记物(CD44+/CD24-),使用流式细胞术评估 VCR 硫酸盐-Exo 的靶向效果。我们的结果表明,VCR 硫酸盐-Exo 的细胞毒性与游离 VCR 硫酸盐几乎相同。流式细胞术分析表明,VRC 硫酸盐-Exo 比游离 VCR 硫酸盐更有效地靶向 MSCs。我们的研究表明,将 VCR 硫酸盐加载到 MSCs 衍生的外泌体中可以改善其靶向递送并减轻其副作用。需要进一步研究来确定 VCR 硫酸盐-Exo 的体内有效性和安全性,并改进其加载和递送策略。