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

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.