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

Shin-Woo Ha,1,2,* Kihwan Hwang,3,* Jun Jin,3 Ae-Sin Cho,1 Tae Yoon Kim,1,2 Sung Il Hwang,1 Hak Jong Lee,1–2,4–5 Chae-Yong Kim3,61Department of Radiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13605, South Korea; 2Resea...

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Autores principales:	Ha SW, Hwang K, Jin J, Cho AS, Kim TY, Hwang SI, Lee HJ, Kim CY
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Blood-Brain Barrier Ultrasound Nanoparticle Microbubble Complex Drug delivery Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/119fde69f7da4213b3f15d84c5e2d48a
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spelling	oai:doaj.org-article:119fde69f7da4213b3f15d84c5e2d48a2021-12-02T07:01:31ZUltrasound-sensitizing nanoparticle complex for overcoming the blood-brain barrier: an effective drug delivery system1178-2013https://doaj.org/article/119fde69f7da4213b3f15d84c5e2d48a2019-05-01T00:00:00Zhttps://www.dovepress.com/ultrasound-sensitizing-nanoparticle-complex-for-overcoming-the-blood-b-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Shin-Woo Ha,1,2,* Kihwan Hwang,3,* Jun Jin,3 Ae-Sin Cho,1 Tae Yoon Kim,1,2 Sung Il Hwang,1 Hak Jong Lee,1–2,4–5 Chae-Yong Kim3,61Department of Radiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13605, South Korea; 2Research Institute, IMGT Co., Ltd, Seongnam, 13605, South Korea; 3Department of Neurosurgery, Seoul National University Bundang Hospital, Seongnam-si, South Korea; 4Department of Nanoconvergence, Seoul National University Graduate School of Convergence Science and Technology, Seoul, South Korea; 5Research Strategy and Management Division and Medical Device R&D Center, Seoul National University Bundang Hospital, Seongnam 13605, South Korea; 6Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea*These authors contributed equally to this workBackground: 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.Keywords: blood–brain barrier, ultrasound, nanoparticle, microbubble, complex, drug deliveryHa SWHwang KJin JCho ASKim TYHwang SILee HJKim CYDove Medical PressarticleBlood-Brain BarrierUltrasoundNanoparticleMicrobubbleComplexDrug deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 3743-3752 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Blood-Brain Barrier Ultrasound Nanoparticle Microbubble Complex Drug delivery Medicine (General) R5-920
spellingShingle	Blood-Brain Barrier Ultrasound Nanoparticle Microbubble Complex Drug delivery Medicine (General) R5-920 Ha SW Hwang K Jin J Cho AS Kim TY Hwang SI Lee HJ Kim CY Ultrasound-sensitizing nanoparticle complex for overcoming the blood-brain barrier: an effective drug delivery system
description	Shin-Woo Ha,1,2,* Kihwan Hwang,3,* Jun Jin,3 Ae-Sin Cho,1 Tae Yoon Kim,1,2 Sung Il Hwang,1 Hak Jong Lee,1–2,4–5 Chae-Yong Kim3,61Department of Radiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13605, South Korea; 2Research Institute, IMGT Co., Ltd, Seongnam, 13605, South Korea; 3Department of Neurosurgery, Seoul National University Bundang Hospital, Seongnam-si, South Korea; 4Department of Nanoconvergence, Seoul National University Graduate School of Convergence Science and Technology, Seoul, South Korea; 5Research Strategy and Management Division and Medical Device R&D Center, Seoul National University Bundang Hospital, Seongnam 13605, South Korea; 6Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University, Seoul, South Korea*These authors contributed equally to this workBackground: 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.Keywords: blood–brain barrier, ultrasound, nanoparticle, microbubble, complex, drug delivery
format	article
author	Ha SW Hwang K Jin J Cho AS Kim TY Hwang SI Lee HJ Kim CY
author_facet	Ha SW Hwang K Jin J Cho AS Kim TY Hwang SI Lee HJ Kim CY
author_sort	Ha SW
title	Ultrasound-sensitizing nanoparticle complex for overcoming the blood-brain barrier: an effective drug delivery system
title_short	Ultrasound-sensitizing nanoparticle complex for overcoming the blood-brain barrier: an effective drug delivery system
title_full	Ultrasound-sensitizing nanoparticle complex for overcoming the blood-brain barrier: an effective drug delivery system
title_fullStr	Ultrasound-sensitizing nanoparticle complex for overcoming the blood-brain barrier: an effective drug delivery system
title_full_unstemmed	Ultrasound-sensitizing nanoparticle complex for overcoming the blood-brain barrier: an effective drug delivery system
title_sort	ultrasound-sensitizing nanoparticle complex for overcoming the blood-brain barrier: an effective drug delivery system
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/119fde69f7da4213b3f15d84c5e2d48a
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Ultrasound-sensitizing nanoparticle complex for overcoming the blood-brain barrier: an effective drug delivery system

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