Dual-frequency ultrasound activation of nanomicellar doxorubicin in targeted tumor chemotherapy

Introduction This study investigated the therapeutic effect of dual-frequency sonication (3 MHz and 28 kHz) at low intensity levels in combination with micellar doxorubicin in the treatment of a tumor model of spontaneous breast adenocarcinoma in Balb/c mice. Methods We used sonication frequencies 2...

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Veröffentlicht in:Journal of medical ultrasonics (2001) 2014-04, Vol.41 (2), p.139-150
Hauptverfasser: Hasanzadeh, Hadi, Mokhtari-Dizaji, Manijhe, Zahra Bathaie, S., Hassan, Zuhair M., Shahbazfar, Amir Ali
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container_issue 2
container_start_page 139
container_title Journal of medical ultrasonics (2001)
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creator Hasanzadeh, Hadi
Mokhtari-Dizaji, Manijhe
Zahra Bathaie, S.
Hassan, Zuhair M.
Shahbazfar, Amir Ali
description Introduction This study investigated the therapeutic effect of dual-frequency sonication (3 MHz and 28 kHz) at low intensity levels in combination with micellar doxorubicin in the treatment of a tumor model of spontaneous breast adenocarcinoma in Balb/c mice. Methods We used sonication frequencies 28 kHz and 3 MHz and their dual combinations in the progressive wave mode to enhance acoustic cavitation. Then, the antitumor effect of the simultaneous dual-frequency ultrasound (28 kHz and 3 MHz) at low intensity levels in combination with doxorubicin and micellar doxorubicin injection was investigated in a spontaneous model of breast adenocarcinoma in Balb/c mice. Sixty-three tumor-bearing mice were randomly divided into seven groups: control, sham, sonication with dual frequency, doxorubicin without sonication, doxorubicin with dual-frequency sonication, micellar doxorubicin without sonication, and micellar doxorubicin with dual-frequency sonication. The tumor volume change relative to the initial volume, tumor growth inhibition ratio, the required times for each tumor to reach two ( T 2 ) and five ( T 5 ) times its initial volume, and survival period were the tumor growth delay parameters which were calculated and recorded at various times after treatment. Results The results of the combination of frequencies 28 kHz (0.04 W/cm 2 ) and 3 MHz (2.00 W/cm 2 ) showed remarkable enhancement of the cavitation activity compared with single-frequency sonication ( P  
doi_str_mv 10.1007/s10396-013-0484-x
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Methods We used sonication frequencies 28 kHz and 3 MHz and their dual combinations in the progressive wave mode to enhance acoustic cavitation. Then, the antitumor effect of the simultaneous dual-frequency ultrasound (28 kHz and 3 MHz) at low intensity levels in combination with doxorubicin and micellar doxorubicin injection was investigated in a spontaneous model of breast adenocarcinoma in Balb/c mice. Sixty-three tumor-bearing mice were randomly divided into seven groups: control, sham, sonication with dual frequency, doxorubicin without sonication, doxorubicin with dual-frequency sonication, micellar doxorubicin without sonication, and micellar doxorubicin with dual-frequency sonication. The tumor volume change relative to the initial volume, tumor growth inhibition ratio, the required times for each tumor to reach two ( T 2 ) and five ( T 5 ) times its initial volume, and survival period were the tumor growth delay parameters which were calculated and recorded at various times after treatment. Results The results of the combination of frequencies 28 kHz (0.04 W/cm 2 ) and 3 MHz (2.00 W/cm 2 ) showed remarkable enhancement of the cavitation activity compared with single-frequency sonication ( P  &lt; 0.05). The micellar doxorubicin injection with sonication group showed a significant difference in the relative volume percent parameter compared with the other groups ( P  &lt; 0.05). Additionally, the T 2 and T 5 times in the micellar doxorubicin with sonication group were significantly higher than in the other groups ( P  &lt; 0.05). Also, the survival period of the mice in the micellar doxorubicin with sonication group was significantly longer than in the other groups ( P  &lt; 0.05). These findings were verified histopathologically. Conclusion This study shows that simultaneous combined dual-frequency ultrasound sonication in continuous mode is effective in producing cavitation activity at low intensity. We conclude that dual-frequency sonication with micellar doxorubicin injection extends survival in a murine breast adenocarcinoma model.</description><identifier>ISSN: 1346-4523</identifier><identifier>EISSN: 1613-2254</identifier><identifier>DOI: 10.1007/s10396-013-0484-x</identifier><identifier>PMID: 27277765</identifier><language>eng</language><publisher>Tokyo: Springer Japan</publisher><subject>Acoustics ; Analysis ; Anticancer properties ; Breast ; Breast cancer ; Cancer ; Cavitation ; Chemotherapy ; Doxorubicin ; Fourier transforms ; Health aspects ; Imaging ; Mathematical models ; Medicine ; Medicine &amp; Public Health ; Nitrogen ; Original Article ; Parameters ; Radiation ; Radiology ; Spectrum analysis ; Survival ; Tumors ; Ultrasonic imaging ; Ultrasound</subject><ispartof>Journal of medical ultrasonics (2001), 2014-04, Vol.41 (2), p.139-150</ispartof><rights>The Japan Society of Ultrasonics in Medicine 2013</rights><rights>COPYRIGHT 2014 Springer</rights><rights>The Japan Society of Ultrasonics in Medicine 2013.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-9d4c592e4963faa67fbcf149fa338fcbc6c9f53c7cabe7ab65587e532a0407a73</citedby><cites>FETCH-LOGICAL-c463t-9d4c592e4963faa67fbcf149fa338fcbc6c9f53c7cabe7ab65587e532a0407a73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10396-013-0484-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2918187483?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,21388,21389,27924,27925,33530,33531,33744,33745,41488,42557,43659,43805,51319,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27277765$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hasanzadeh, Hadi</creatorcontrib><creatorcontrib>Mokhtari-Dizaji, Manijhe</creatorcontrib><creatorcontrib>Zahra Bathaie, S.</creatorcontrib><creatorcontrib>Hassan, Zuhair M.</creatorcontrib><creatorcontrib>Shahbazfar, Amir Ali</creatorcontrib><title>Dual-frequency ultrasound activation of nanomicellar doxorubicin in targeted tumor chemotherapy</title><title>Journal of medical ultrasonics (2001)</title><addtitle>J Med Ultrasonics</addtitle><addtitle>J Med Ultrason (2001)</addtitle><description>Introduction This study investigated the therapeutic effect of dual-frequency sonication (3 MHz and 28 kHz) at low intensity levels in combination with micellar doxorubicin in the treatment of a tumor model of spontaneous breast adenocarcinoma in Balb/c mice. Methods We used sonication frequencies 28 kHz and 3 MHz and their dual combinations in the progressive wave mode to enhance acoustic cavitation. Then, the antitumor effect of the simultaneous dual-frequency ultrasound (28 kHz and 3 MHz) at low intensity levels in combination with doxorubicin and micellar doxorubicin injection was investigated in a spontaneous model of breast adenocarcinoma in Balb/c mice. Sixty-three tumor-bearing mice were randomly divided into seven groups: control, sham, sonication with dual frequency, doxorubicin without sonication, doxorubicin with dual-frequency sonication, micellar doxorubicin without sonication, and micellar doxorubicin with dual-frequency sonication. The tumor volume change relative to the initial volume, tumor growth inhibition ratio, the required times for each tumor to reach two ( T 2 ) and five ( T 5 ) times its initial volume, and survival period were the tumor growth delay parameters which were calculated and recorded at various times after treatment. Results The results of the combination of frequencies 28 kHz (0.04 W/cm 2 ) and 3 MHz (2.00 W/cm 2 ) showed remarkable enhancement of the cavitation activity compared with single-frequency sonication ( P  &lt; 0.05). The micellar doxorubicin injection with sonication group showed a significant difference in the relative volume percent parameter compared with the other groups ( P  &lt; 0.05). Additionally, the T 2 and T 5 times in the micellar doxorubicin with sonication group were significantly higher than in the other groups ( P  &lt; 0.05). Also, the survival period of the mice in the micellar doxorubicin with sonication group was significantly longer than in the other groups ( P  &lt; 0.05). These findings were verified histopathologically. Conclusion This study shows that simultaneous combined dual-frequency ultrasound sonication in continuous mode is effective in producing cavitation activity at low intensity. 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Methods We used sonication frequencies 28 kHz and 3 MHz and their dual combinations in the progressive wave mode to enhance acoustic cavitation. Then, the antitumor effect of the simultaneous dual-frequency ultrasound (28 kHz and 3 MHz) at low intensity levels in combination with doxorubicin and micellar doxorubicin injection was investigated in a spontaneous model of breast adenocarcinoma in Balb/c mice. Sixty-three tumor-bearing mice were randomly divided into seven groups: control, sham, sonication with dual frequency, doxorubicin without sonication, doxorubicin with dual-frequency sonication, micellar doxorubicin without sonication, and micellar doxorubicin with dual-frequency sonication. The tumor volume change relative to the initial volume, tumor growth inhibition ratio, the required times for each tumor to reach two ( T 2 ) and five ( T 5 ) times its initial volume, and survival period were the tumor growth delay parameters which were calculated and recorded at various times after treatment. Results The results of the combination of frequencies 28 kHz (0.04 W/cm 2 ) and 3 MHz (2.00 W/cm 2 ) showed remarkable enhancement of the cavitation activity compared with single-frequency sonication ( P  &lt; 0.05). The micellar doxorubicin injection with sonication group showed a significant difference in the relative volume percent parameter compared with the other groups ( P  &lt; 0.05). Additionally, the T 2 and T 5 times in the micellar doxorubicin with sonication group were significantly higher than in the other groups ( P  &lt; 0.05). Also, the survival period of the mice in the micellar doxorubicin with sonication group was significantly longer than in the other groups ( P  &lt; 0.05). These findings were verified histopathologically. Conclusion This study shows that simultaneous combined dual-frequency ultrasound sonication in continuous mode is effective in producing cavitation activity at low intensity. We conclude that dual-frequency sonication with micellar doxorubicin injection extends survival in a murine breast adenocarcinoma model.</abstract><cop>Tokyo</cop><pub>Springer Japan</pub><pmid>27277765</pmid><doi>10.1007/s10396-013-0484-x</doi><tpages>12</tpages></addata></record>
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subjects Acoustics
Analysis
Anticancer properties
Breast
Breast cancer
Cancer
Cavitation
Chemotherapy
Doxorubicin
Fourier transforms
Health aspects
Imaging
Mathematical models
Medicine
Medicine & Public Health
Nitrogen
Original Article
Parameters
Radiation
Radiology
Spectrum analysis
Survival
Tumors
Ultrasonic imaging
Ultrasound
title Dual-frequency ultrasound activation of nanomicellar doxorubicin in targeted tumor chemotherapy
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