Ultrasound-irradiated bindable microbomb opens the blood-brain barrier to enhance glioma therapy

• Published in: Nano today 2024-06, Vol.56, p.102312, Article 102312
• Main Authors: Li, Bo, Zhong, Huihai, Wei, Huiye, Chen, Gengjia, Lin, Minzhao, Huang, Sicong, Zhang, Qiaoyun, Xing, Chengfen, Li, Tan, Huang, Jinsheng, Shuai, Xintao
• Format: Article
• Language: English
• Subjects: Blood-brain barrier; Drug delivery; Glioma therapy; Microbubble; Ultrasound
• ISSN: 1748-0132; 1878-044X
• DOI: 10.1016/j.nantod.2024.102312

Few effective treatments are available for gliomas nowadays because the tank armor-like blood-brain barrier (BBB) impedes drug penetration into the brain and the indistinguishable tumor boundary makes surgical resection inefficient. Aiming to solve this problem, we herein utilized a BBB-bindable microbubble decorated with an ApoE peptide for specific binding to low-density lipoprotein receptors predominantly expressed on brain capillary endothelial cells as an intracranial drug delivery system. Surface siloxane bonds reinforced the stability of the microbubble during circulation in the bloodstream. Consequently, the microbubble accumulated on the walls of brain microvessels, thus opening the tank-armored BBB therein via a microbomb effect after the implementation of ultrasound irradiation. Compared with the clinically available microbubbles (e.g. SonoVue) that quickly pass the brain microvessel wall, this BBB-bindable microbubble effectively opened the BBB with a much lower risk of brain damage. Thus, approximately 7% of the payloads including temozolomide and a newly synthesized glioma-targeting molecular probe were delivered into the brain tumor site after systematical injection, which not only identified the tumor boundary but also remarkably inhibited orthotopic glioma growth in mice. Overall, this tailor-made microbomb offers tremendous opportunities for effective intracranial drug delivery against gliomas. [Display omitted] •The microbomb was able to bind on brain microvessels, thus opening the BBB therein with a much lower risk of brain damage.•The microbomb's surface was reinforced with siloxane bonds to enhance its stability during blood circulation.•A molecular probe was synthesized to identify the indistinguishable boundary between the glioma and the normal brain tissue.