Ultrasound sonication with microbubbles disrupts blood vessels and enhances tumor treatments of anticancer nanodrug

Chung-Yin Lin1*, Hsiao-Ching Tseng1*, Heng-Ruei Shiu1, Ming-Fang Wu2, Cheng-Ying Chou3, Win-Li Lin1,41Institute of Biomedical Engineering, 2Laboratory Animal Center, 3Department of Bio-Industrial Mechatronics Engineering, National Taiwan University, Taipei, Taiwan; 4Division of Medical Engineering R...

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Autores principales:	Lin CY, Tseng HC, Shiu HR, Wu MF, Chou CY, Lin WL
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/1953f3392430491098c0ea594c1f0585
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spelling	oai:doaj.org-article:1953f3392430491098c0ea594c1f05852021-12-02T06:16:08ZUltrasound sonication with microbubbles disrupts blood vessels and enhances tumor treatments of anticancer nanodrug1176-91141178-2013https://doaj.org/article/1953f3392430491098c0ea594c1f05852012-04-01T00:00:00Zhttp://www.dovepress.com/ultrasound-sonication-with-microbubbles-disrupts-blood-vessels-and-enh-a9757https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Chung-Yin Lin1, Hsiao-Ching Tseng1, Heng-Ruei Shiu1, Ming-Fang Wu2, Cheng-Ying Chou3, Win-Li Lin1,41Institute of Biomedical Engineering, 2Laboratory Animal Center, 3Department of Bio-Industrial Mechatronics Engineering, National Taiwan University, Taipei, Taiwan; 4Division of Medical Engineering Research, National Health Research Institutes, Miaoli, Taiwan*These authors contributed equally to this workAbstract: Ultrasound (US) sonication with microbubbles (MBs) has the potential to disrupt blood vessels and enhance the delivery of drugs into the sonicated tissues. In this study, mouse ear tumors were employed to investigate the therapeutic effects of US, MBs, and pegylated liposomal doxorubicin (PLD) on tumors. Tumors started to receive treatments when they grew up to about 15 mm3 (early stage) with injection of PLD 10 mg/kg, or up to 50 mm3 (medium stage) with PLD 6 (or 4) mg/kg. Experiments included the control, PLD alone, PLD + MBs + US, US alone, and MBs + US groups. The procedure for the PLD + MBs + US group was that PLD was injected first, MB (SonoVue) injection followed, and then US was immediately sonicated on the tumor. The results showed that: (1) US sonication with MBs was always able to produce a further hindrance to tumor growth for both early and medium-stage tumors; (2) for the medium-stage tumors, 6 mg/kg PLD alone was able to inhibit their growth, while it did not work for 4 mg/kg PLD alone; (3) with the application of MBs + US, 4 mg/kg PLD was able to inhibit the growth of medium-stage tumors; (4) for early stage tumors after the first treatment with a high dose of PLD alone (10 mg/kg), the tumor size still increased for several days and then decreased (a biphasic pattern); (5) MBs + US alone was able to hinder the growth of early stage tumors, but unable to hinder that of medium stage tumors. The results of histological examinations and blood perfusion measurements indicated that the application of MBs + US disrupts the tumor blood vessels and enhances the delivery of PLD into tumors to significantly inhibit tumor growth.Keywords: ultrasound, microbubbles, nanodrug, mouse tumor, vascular disruption, tumor growth responseLin CYTseng HCShiu HRWu MFChou CYLin WLDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 2143-2152 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Lin CY Tseng HC Shiu HR Wu MF Chou CY Lin WL Ultrasound sonication with microbubbles disrupts blood vessels and enhances tumor treatments of anticancer nanodrug
description	Chung-Yin Lin1, Hsiao-Ching Tseng1, Heng-Ruei Shiu1, Ming-Fang Wu2, Cheng-Ying Chou3, Win-Li Lin1,41Institute of Biomedical Engineering, 2Laboratory Animal Center, 3Department of Bio-Industrial Mechatronics Engineering, National Taiwan University, Taipei, Taiwan; 4Division of Medical Engineering Research, National Health Research Institutes, Miaoli, Taiwan*These authors contributed equally to this workAbstract: Ultrasound (US) sonication with microbubbles (MBs) has the potential to disrupt blood vessels and enhance the delivery of drugs into the sonicated tissues. In this study, mouse ear tumors were employed to investigate the therapeutic effects of US, MBs, and pegylated liposomal doxorubicin (PLD) on tumors. Tumors started to receive treatments when they grew up to about 15 mm3 (early stage) with injection of PLD 10 mg/kg, or up to 50 mm3 (medium stage) with PLD 6 (or 4) mg/kg. Experiments included the control, PLD alone, PLD + MBs + US, US alone, and MBs + US groups. The procedure for the PLD + MBs + US group was that PLD was injected first, MB (SonoVue) injection followed, and then US was immediately sonicated on the tumor. The results showed that: (1) US sonication with MBs was always able to produce a further hindrance to tumor growth for both early and medium-stage tumors; (2) for the medium-stage tumors, 6 mg/kg PLD alone was able to inhibit their growth, while it did not work for 4 mg/kg PLD alone; (3) with the application of MBs + US, 4 mg/kg PLD was able to inhibit the growth of medium-stage tumors; (4) for early stage tumors after the first treatment with a high dose of PLD alone (10 mg/kg), the tumor size still increased for several days and then decreased (a biphasic pattern); (5) MBs + US alone was able to hinder the growth of early stage tumors, but unable to hinder that of medium stage tumors. The results of histological examinations and blood perfusion measurements indicated that the application of MBs + US disrupts the tumor blood vessels and enhances the delivery of PLD into tumors to significantly inhibit tumor growth.Keywords: ultrasound, microbubbles, nanodrug, mouse tumor, vascular disruption, tumor growth response
format	article
author	Lin CY Tseng HC Shiu HR Wu MF Chou CY Lin WL
author_facet	Lin CY Tseng HC Shiu HR Wu MF Chou CY Lin WL
author_sort	Lin CY
title	Ultrasound sonication with microbubbles disrupts blood vessels and enhances tumor treatments of anticancer nanodrug
title_short	Ultrasound sonication with microbubbles disrupts blood vessels and enhances tumor treatments of anticancer nanodrug
title_full	Ultrasound sonication with microbubbles disrupts blood vessels and enhances tumor treatments of anticancer nanodrug
title_fullStr	Ultrasound sonication with microbubbles disrupts blood vessels and enhances tumor treatments of anticancer nanodrug
title_full_unstemmed	Ultrasound sonication with microbubbles disrupts blood vessels and enhances tumor treatments of anticancer nanodrug
title_sort	ultrasound sonication with microbubbles disrupts blood vessels and enhances tumor treatments of anticancer nanodrug
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/1953f3392430491098c0ea594c1f0585
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Ultrasound sonication with microbubbles disrupts blood vessels and enhances tumor treatments of anticancer nanodrug

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