In a groundbreaking study published in the *Journal of Nanobiotechnology*, researchers have demonstrated a novel approach to combat medulloblastoma metastasis using targeted extracellular vesicles (EVs) and focused ultrasound technology. This research, led by Anh Duy Do from the Department of Physiology, Pathophysiology and Immunology at Pham Ngoc Thach University of Medicine, offers a promising avenue for improving the treatment of this aggressive pediatric brain tumor.
Medulloblastoma, a highly metastatic brain tumor, is notoriously difficult to treat and is the leading cause of death in children with this condition. Current treatments often rely on radiotherapy, which, while effective, can lead to long-term neurocognitive deficits. The need for innovative, targeted therapies has never been more pressing.
The study introduces a sophisticated model of RNA therapy using targeted EVs to deliver therapeutic small-interfering (si)RNAs directly to medulloblastoma cells. “We engineered EVs to express an MB-specific peptide, E1-3, which significantly enhanced their internalization into medulloblastoma cells,” explains Do. This targeted approach ensures that the therapeutic siRNAs are delivered precisely where they are needed, minimizing off-target effects.
The researchers loaded these MB-targeted EVs (MB-tEVs) with siRNAs designed to silence LOXL1-AS1, a pro-metastatic long non-coding RNA found in sonic-hedgehog medulloblastoma (SHH-MB). In vitro experiments showed that the delivered siRNAs effectively silenced LOXL1-AS1, suppressing metastatic traits in SHH-MB cells.
To further improve the delivery of these therapeutic EVs to the brain, the researchers employed microbubble-enhanced focused ultrasound (FUS). This technique enhances the accumulation of systemically injected EVs in the brain, making the treatment more effective.
In an orthotopic mouse model of SHH-MB, mice treated with siRNA-loaded MB-tEVs showed decreased LOXL1-AS1 expression, reduced metastases, and improved survival rates. “Our findings provide the first evidence for the combined use of tumor-targeted EVs and microbubble-enhanced FUS to deliver therapeutic siRNAs to suppress metastatic medulloblastoma,” Do notes. “This approach has the potential to support conventional treatments and improve clinical outcomes for this malignant pediatric tumor.”
The implications of this research extend beyond the immediate application in medulloblastoma treatment. The use of targeted EVs and focused ultrasound technology could pave the way for more precise and effective delivery of therapeutic agents to other types of cancers and neurological disorders. This could revolutionize the field of targeted therapy, offering new hope for patients and their families.
As the research continues to evolve, the potential for commercial impact in the biotechnology and pharmaceutical sectors is substantial. Companies specializing in nanotechnology and targeted drug delivery could see significant growth as this technology moves from the lab to the clinic. The integration of focused ultrasound technology with targeted EV delivery represents a paradigm shift in how we approach the treatment of complex diseases.
In conclusion, this study highlights the transformative potential of combining targeted extracellular vesicles with focused ultrasound technology to deliver therapeutic siRNAs. As Anh Duy Do and his team continue to refine this approach, the future of targeted therapy looks brighter than ever. The research, published in the *Journal of Nanobiotechnology* (translated to English as *Journal of Nanobiotechnology*), marks a significant step forward in the fight against medulloblastoma and other metastatic cancers.