<p>Ultrasound-sensitizing nanoparticle complex for overcoming the blood-brain barrier: an effective drug delivery system</p>

Abstract

Background: Crossing the blood–brain barrier (BBB) is crucial for drug delivery to the brain and for treatment of brain tumors, such as glioblastoma, the most common of all primary malignant brain tumors. Microbubble (MB) is oscillated and destroyed by controlling ultrasound (US) parameters. This oscillation and destruction of MB can open the BBB transiently, and a drug can be delivered to the brain. Materials and methods: For testing the efficiency of delivery to the brain, we synthesized a US-sensitizing nanoparticle (NP) complex via chemically binding MBs and NPs for the BBB opening, including near-infrared dye-incorporated albumin nanoparticles (NIR-Alb NPs) for fluorescence detection. Results: The human-derived, biocompatible NIR-Alb NPs did not show significant cytotoxicity to 500 μg/mL for 3 days in four human glioma cell lines. In an in vivo animal study, some US parameters were investigated to determine optimal conditions. The optimized US conditions were applied in a U87MG orthotopic mouse model. We found that the fluorescence intensity in the brain was 1.5 times higher than in the control group. Conclusion: Our US-sensitizing NP complex and US technique could become one of the critical technologies for drug delivery to the brain.

Recent Advances on Ultrasound Contrast Agents for Blood-Brain Barrier Opening with Focused Ultrasound

“…Finally, Ha et al proposed a drug delivery system by binding microbubble with ultrasound-sensitizing dye-incorporating nanoparticles. They successfully delivered those nanoparticles to the U87MG (human glioblastoma cell line) located in the mouse brain (fluorescence intensity 1.5 times higher than the control group) [ 90 ].…”

Recent progress in nanomedicines for imaging and therapy of brain tumors

“…In an in vivo orthotopic mouse model, NIR-Alb NP's fluorescence intensity in the brain was 1.5 times higher compared to that in the control group. 50 For example, Li, Yujie et al (2021) illustrated the development of a neutrophil-delivered nanosensitizer with ultrasound augmented chemo/immunotherapy for GBM. The composition of ZnGa 2 O 4 :Cr 3+ (ZGO) with TiO 2 to form ZGO@TiO 2 helped to control the drug release.…”

Microbubble Delivery Platform for Ultrasound-Mediated Therapy in Brain Cancers

“…The host-guest interaction of avidin-biotin was used to modify the targeting ligand on the MBs’ surface ( Scheme 2 c) [ 62 , 65 ]. Because the surface area or shell volume of the MBs is restricted, modification of the liposomes on the MBs’ surface provides a larger space for accommodating medicinal materials ( Scheme 2 d) [ 28 , 66 , 67 , 68 , 69 , 70 ].…”