Engineering and Characterization of an Artificial Drug‐Carrying Vesicles Nanoplatform for Enhanced Specifically Targeted Therapy of Glioblastoma

Abstract

AbstractGlioblastoma multiforme (GBM) treatment is hindered by complex pathologies and the need to cross the blood–brain barrier (BBB) during drug delivery. Although exosomes have great potential for GBM treatment, these alone cannot fully meet the therapeutic requirements, owing to their limitations in targeting and delivery. Herein, engineered artificial vesicles (EAVs), ANG‐TRP‐PK1@EAVs, which are constructed using a liposome extruder from HEK293T cells expressing ANG‐TRP‐PK1 peptides, is developed. ANG‐TRP‐PK1 is a fusion peptide of Angiopep‐2 fused to the N‐terminus of TRP‐PK1, to present Angiopep‐2 on the EAVs. ANG‐TRP‐PK1@EAVs have similar characteristics to the secreted exosomes, but a much higher yield. ANG‐TRP‐PK1@EAVs have efficient BBB‐penetration and GBM‐targeting abilities in a mock BBB model in in vitro and orthotopic GBM mouse models in vivo. Doxorubicin loading EAVs (ANG‐TRP‐PK1@DOX) do not alter the characteristics of the EAVs, which can cross the BBB, reach the GBM, and kill tumor cells in orthotopic GBM mouse models. These engineered drug‐loaded artificial vesicles show better therapeutic effects on GBM than temozolomide in mice, with very few side effects. In conclusion, EAVs can be inserted into different targeting ligands and packed into different drugs, and they may serve as unique and efficient nanoplatforms for drug delivery and tumor promise therapy.