Shandong Center For Food and Drug Evaluation & Inspection, Jinan, China.
Zibo Food and Drug Inspection and Research Institute, Zibo, China.
Kaohsiung J Med Sci. 2024 May;40(5):435-444. doi: 10.1002/kjm2.12819. Epub 2024 Mar 14.
A direct strategy to achieve specific treatments and reduce side effects is through cell type-specific drug delivery. Exosomes (Exos) can be modified with folic acid (FA) to prepare drug delivery systems targeting tumor cells that highly express FA receptors. This study aimed to produce an exo drug delivery system with FA decoration and temozolomide (TMZ) loading to improve the sustained TMZ release and targeting. We used DSPE-PEG-FA to modify exos derived from astrocyte U-87 to prepare FA-modified exos (Astro-exo-FA). TMZ was encapsulated into Astro-exo-FA or Astro-exo through electroporation to produce TMZ@Astro-exo and TMZ@Astro-exo-FA. In vitro drug release was examined using the dialysis bag method. Through cell experiments in vitro and mouse glioma models in vivo, the effect of TMZ@Astro-exo-FA on U-87 cells was determined. Exo properties were not affected by FA modification and TMZ loading. The drug release rate of TMZ@Astro-exo-FA was slower. TMZ@Astro-exo-FA uptake by U-87 cells was higher compared to TMZ@Astro-exo, indicating that TMZ@Astro-exo-FA has a stronger targeting toward U-87 cells. TMZ@Astro-exo-FA remarkably reduced U-87 cell proliferation, migration, and invasion compared with TMZ@Astro-exo and free TMZ. Treatment with TMZ@Astro-exo-FA reduced the side effects of TMZ (minimal change in body weight), prolonged survival, and inhibited tumor growth in mouse glioma models, and its efficacy was stronger than that of TMZ@Astro-exo and free TMZ. TMZ@Astro-exo-FA could enhance the effect of TMZ against glioma, providing novel ideas for drug targeting delivery and exploring exos as drug carriers against glioma.
一种实现特定治疗和减少副作用的直接策略是通过细胞类型特异性药物传递。外泌体（Exos）可以用叶酸（FA）修饰，以制备针对高表达 FA 受体的肿瘤细胞的药物传递系统。本研究旨在制备具有 FA 修饰和替莫唑胺（TMZ）负载的外泌体药物传递系统，以改善 TMZ 的持续释放和靶向性。我们使用 DSPE-PEG-FA 修饰星形胶质细胞 U-87 来源的外泌体，制备 FA 修饰的外泌体（Astro-exo-FA）。通过电穿孔将 TMZ 包裹到 Astro-exo-FA 或 Astro-exo 中，制备 TMZ@Astro-exo 和 TMZ@Astro-exo-FA。采用透析袋法检测体外药物释放情况。通过体外细胞实验和体内小鼠脑胶质瘤模型，研究 TMZ@Astro-exo-FA 对 U-87 细胞的作用。FA 修饰和 TMZ 负载对外泌体性质没有影响。TMZ@Astro-exo-FA 的药物释放速率较慢。与 TMZ@Astro-exo 相比，U-87 细胞对 TMZ@Astro-exo-FA 的摄取更高，表明 TMZ@Astro-exo-FA 对 U-87 细胞具有更强的靶向性。与 TMZ@Astro-exo 和游离 TMZ 相比，TMZ@Astro-exo-FA 显著降低了 U-87 细胞的增殖、迁移和侵袭。TMZ@Astro-exo-FA 治疗可减轻 TMZ 的副作用（体重变化最小），延长生存期，并抑制小鼠脑胶质瘤模型中的肿瘤生长，其疗效强于 TMZ@Astro-exo 和游离 TMZ。TMZ@Astro-exo-FA 可增强 TMZ 对脑胶质瘤的作用，为药物靶向递送提供了新的思路，并探索了外泌体作为脑胶质瘤的药物载体。
