Folic acid-decorated astrocytes-derived exosomes enhanced the effect of temozolomide against glioma.

Abstract

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-PEG₂₀₀₀-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.