ArticleJournal of nanobiotechnology2025
Delivery of LOXL1-AS1-siRNAs using targeting peptide-engineered extracellular vesicles with focused ultrasound to suppress medulloblastoma metastasis.
Article in Journal of nanobiotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Engineered Exosomes in Precision Neuro-Oncology: Mechanisms, Therapeutics, and Translational Challenges.Cancers · 2026Review
- Focused ultrasound for cellular mechanoactivation and nanomedicine delivery in cancer.Biomedical microdevices · 2026Review
- Locoregional Delivery of miRNAs for Glioblastoma Treatment: A Systematic Review of Advances in Delivery Systems.Pharmaceutics · 2026Review
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Authors and funding
9 authors.
Funding
Abstract
backgroundMetastasis of medulloblastomas (MBs) is difficult to treat and remains the primary cause of death in children with this brain tumor. Current treatment focuses on radiotherapy to limit metastatic recurrence and maintain survival, but this may cause long-term neurocognitive deficits. This challenge emphasizes the need for novel targeted therapies to combat metastatic MB. In this study, we report an RNA therapy model using targeted extracellular vesicles (EVs) to deliver therapeutic small-interfering (si)RNAs to MB.
resultsFirst, MB-targeted EVs (MB-tEVs) were generated via genetic modification of EV-producing cells to express E1-3, an MB-specific peptide. Next, isolated MB-tEVs were loaded with siRNAs that targeted LOXL1-AS1, a pro-metastatic long non-coding RNA in sonic-hedgehog MB (SHH-MB). Expression of the E1-3 peptide increased MB-tEV internalization into MB cells, where the delivered siRNAs effectively silenced LOXL1-AS1 and suppressed LOXL1-AS1-mediated metastatic traits of SHH-MB cells in vitro. Locoregional application of microbubble-enhanced focused ultrasound (FUS) improved the accumulation of systemically injected EVs in the mouse brain. Mice treated with siRNA-loaded MB-tEVs had decreased LOXL1-AS1 expression, reduced metastases, and improved survival in an SHH-MB orthotopic model.
conclusionsOur study provides the first and very promising evidence for the combined use of tumor-targeted EVs and microbubble-enhanced FUS to deliver therapeutic siRNAs to suppress metastatic MB, potentially supporting conventional treatments and improving clinical outcomes of this malignant pediatric tumor.
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