Glioma-targeted delivery of exosome-encapsulated antisense oligonucleotides using neural stem cells.

ABSTRACT: Tropism of neural stem cells (NSCs) to hypoxic tumor areas provides an opportunity for the drug delivery. Here, we demonstrate that NSCs effectively transport antisense oligonucleotides (ASOs) targeting oncogenic and tolerogenic signal transducer and activator of transcription 3 (STAT3) protein into glioma microenvironment. To enable spontaneous, scavenger receptor-mediated endocytosis by NSCs, we used previously described CpG-STAT3ASO conjugates. Following uptake and endosomal escape, CpG-STAT3ASO colocalized with CD63⁺ vesicles and later with CD63⁺CD81⁺ exosomes. Over 3 days, NSCs secreted exosomes loaded up to 80% with CpG-STAT3ASO. Compared to native NSC exosomes, the CpG-STAT3ASO-loaded exosomes potently stimulated immune activity of human dendritic ce

SUBMITTER: Adamus T 

PROVIDER: S-EPMC8752899 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature