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Biodegradable Acoustic Targeting for Ultrasound-Supported Gene Therapy (BATUS) in Glioblastoma
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DOI：10.1002/advs.76336.png)
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Abstract
En 中文
Glioblastoma (GBM) remains one of the most challenging brain malignancies due to the restrictive nature of the blood–brain barrier (BBB), which severely limits effective drug and gene delivery. To overcome this, we introduce Biodegradable Acoustic Targeting for Ultrasound-Supported Gene Therapy (BATUS), a modular platform that enables safe, repeated, and targeted gene delivery to the brain. BATUS integrates an implantable, fully biodegradable glycine-based ultrasound (US) transducer, surgically placed via craniotomy for precise BBB opening, along with customizable peptide-targeted liposomal gene carriers. This system combines US-mediated transient BBB disruption with ligand-directed cellular targeting to enable efficient delivery across both vascular and cellular barriers. As a proof-of-concept, BATUS was evaluated using tLyp1-functionalized liposomes carrying PD-L1-targeting siRNA for GBM immunotherapy: in vitro evaluations confirmed efficient siRNA entrapment, stability, and specific cellular uptake, while in vivo studies in orthotopic GL261 GBM mouse models showed enhanced BBB permeability, significant PD-L1 silencing, reduced tumor growth, and prolonged survival. Crucially, BATUS exhibited a favorable safety profile, with no detectable local or systemic toxicity in animal models. By providing a modular framework where targeting ligands and genetic cargo are easily adaptable, BATUS is established as a strategy for precision gene delivery across the BBB, as demonstrated here for GBM.
Keywords:
biodegradable ultrasound transducer
blood–brain barrier opening
glioblastoma immunotherapy
piezoelectric biomaterials
ultrasound-mediated gene delivery
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