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Engineered Exosomes with Ouabain for H3K27M‐Mutated DIPG Therapy.

Engineered Exosomes with Ouabain for H3K27M‐Mutated DIPG Therapy.

Authors :
Shan, Shaobo
Chen, Junge
Qing, Guangchao
Xie, Luyang
Xia, Bozhang
Pan, Changcun
Xu, Cheng
Fang, Hongjuan
Wan, Yichen
Yang, Yun
Fan, Yubo
Liang, Xing‐Jie
Zhang, Liwei
Source :
Advanced Functional Materials. Oct2024, p1. 17p. 9 Illustrations.
Publication Year :
2024

Abstract

Diffuse intrinsic pontine glioma (DIPG) is a highly lethal tumor that occurs in the brain stem. At present, there is no effective drug for DIPG. In this work, Na/K‐ATPase inhibitor‐ouabain (OB) is found to efficiently kill H3K27M‐mutated DIPG at low doses, inhibit tumor cell proliferation, reduce tumor stemness for the first time, demonstrating its potential as a chemotherapy drug for DIPG. In order to increase the blood–brain barrier (BBB) permeability and tumor accumulation of OB, acidic‐responsive engineered exosomes loaded with OB (OB@EXO‐LCCP) are constructed, which increase the accumulation of OB within the tumor microenvironment of DIPG and efficiently deliver OB to DIPG cells to achieve targeted killing effect. In in vitro experiments, OB@EXO‐LCCP is able to release OB in an acid‐responsive manner and effectively kill DIPG tumor cells. In in vivo experiments, OB@EXO‐LCCP significantly inhibits DIPG growth and prolongs the overall survival of DIPG‐bearing mice. Overall, OB@EXO‐LCCP can promote the BBB permeability and tumor‐targeting ability of OB, thereby enhancing its DIPG‐killing ability and reducing its toxicity. This study provides technical and theoretical information for the precision therapy of DIPG. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
1616301X
Database :
Academic Search Index
Journal :
Advanced Functional Materials
Publication Type :
Academic Journal
Accession number :
180265364
Full Text :
https://doi.org/10.1002/adfm.202413286