3D-ASC-Exos as a novel drug carrier for glioma treatment.

Introduction: It is known that extracts from deer antler stem cells have an inhibitory effect on glioma growth. Therefore, it is hypothesized that exosomes derived from deer antler stem cells (ASC-Exos) can be used as a new drug carrier for the treatment of glioma.

Methods: To begin with, we established a 3D culture system to obtain more exosomes and characterized the 3D-ASC-Exos. Subsequently, we loaded TMZ into 3D-ASC-Exos. Evaluate the effects of 3D-ASC-Exos loaded with TMZ on glioma cell proliferation, migration, invasion, and apoptosis at the cellular level. Additionally, the safety and efficacy of 3D-ASC-Exos loaded with TMZ against glioma were evaluated using tumor-bearing mice.

Results: Compared with the 2D-ASC-Exos obtained from the traditional 2D culture, the 3D-ASC-Exos obtained from our constructed 3D culture system were concentrated nearly 30 times in the culture medium volume, which was more convenient for subsequent puriffcation. The two forms of ASC-Exos had similar morphologies and surface markers, but 3D-ASC-Exos were enriched with more miRNAs related to tumor suppression. In vitro experiments demonstrated that 3D-ASC-exosomes loaded with temozolomide (TMZ) inhibited the proliferation, migration and invasion abilities of glioma cells and promoted the apoptosis of glioma cells. The vivo tumor-bearing mouse model demonstrated that 3D-ASC-Exos loaded with TMZ exerted tumor-suppressive effects by inhibiting tumor growth and promoting tumor apoptosis. Meanwhile, the treatment with 3D-ASC-Exos loaded with TMZ caused no damage to the various tissues and organs of mice compared with the TMZ group.

Discussion: 3D-ASC-Exos can be used as a novel drug carrier for glioma treatment. The development of 3D-ASC-Exos as a drug carrier not only provides a better strategy for tumor treatment, but also demonstrates the broad potential of exosomes in targeted tumor therapy.