Concurrent Osteosarcoma Theranostic Strategy Using Contrast-Enhanced Ultrasound and Drug-Loaded Bubbles
Osteosarcoma (OS) is the most common bone tumor in children and teenagers. The multidrug resistant property of OS produces a major obstacle to chemotherapy, since the effective drug dose cannot be achieved via conventional drug delivery routes without serious systemic cytotoxicity. Microbubbles in c...
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MDPI AG
2019-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/11/5/223 |
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| author | Tai-Tzung Kuo Chung-Hsin Wang Jir-You Wang Hong-Jen Chiou Ching-Hsiang Fan Chih-Kuang Yeh |
| author_facet | Tai-Tzung Kuo Chung-Hsin Wang Jir-You Wang Hong-Jen Chiou Ching-Hsiang Fan Chih-Kuang Yeh |
| author_sort | Tai-Tzung Kuo |
| collection | DOAJ |
| description | Osteosarcoma (OS) is the most common bone tumor in children and teenagers. The multidrug resistant property of OS produces a major obstacle to chemotherapy, since the effective drug dose cannot be achieved via conventional drug delivery routes without serious systemic cytotoxicity. Microbubbles in conjunction with ultrasound (US) has recently been shown to spatially and temporally permeabilize the cellular membrane, promoting drug penetration into tumors. Here, we investigated whether drug (doxorubicin, DOX)-loaded bubbles (DOX-bubbles) can serve as drug-loaded carriers in combination with US in order to facilitate tumor drug delivery. The proposed bubbles have a high payload capacity (efficiency of 69.4 ± 9.1%, payload of 1.4 mg/mL) for DOX. In vitro data revealed that when used in combination with US (1-MHz), these DOX-bubbles facilitate DOX entering into tumor cells. In tumor-bearing animals, DOX-bubbles + US could provide 3.7-fold suppression of tumor growth compared with the group without insonation (1.8 ± 0.9 cm<sup>3</sup> vs. 8.5 ± 2.2 cm<sup>3</sup>) because of the acceleration of DOX-induced tumor necrosis. In the meantime, the tumor perfusion and volume can be monitored by DOX-bubbles with contrast-enhanced ultrasound imaging. Our data provide useful information in support of translating the use of theranostic US-responsive bubbles for regulated tumor drug delivery into clinical use. |
| first_indexed | 2024-04-11T21:58:57Z |
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| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T21:58:57Z |
| publishDate | 2019-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-e0ea2b964b8d4ff88210a55fb13f4e6d2022-12-22T04:01:00ZengMDPI AGPharmaceutics1999-49232019-05-0111522310.3390/pharmaceutics11050223pharmaceutics11050223Concurrent Osteosarcoma Theranostic Strategy Using Contrast-Enhanced Ultrasound and Drug-Loaded BubblesTai-Tzung Kuo0Chung-Hsin Wang1Jir-You Wang2Hong-Jen Chiou3Ching-Hsiang Fan4Chih-Kuang Yeh5Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, TaiwanDepartment of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, TaiwanDepartment of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei 11217, TaiwanDepartment of Radiology, Taipei-Veterans General Hospital, Taipei 11217, TaiwanDepartment of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, TaiwanDepartment of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, TaiwanOsteosarcoma (OS) is the most common bone tumor in children and teenagers. The multidrug resistant property of OS produces a major obstacle to chemotherapy, since the effective drug dose cannot be achieved via conventional drug delivery routes without serious systemic cytotoxicity. Microbubbles in conjunction with ultrasound (US) has recently been shown to spatially and temporally permeabilize the cellular membrane, promoting drug penetration into tumors. Here, we investigated whether drug (doxorubicin, DOX)-loaded bubbles (DOX-bubbles) can serve as drug-loaded carriers in combination with US in order to facilitate tumor drug delivery. The proposed bubbles have a high payload capacity (efficiency of 69.4 ± 9.1%, payload of 1.4 mg/mL) for DOX. In vitro data revealed that when used in combination with US (1-MHz), these DOX-bubbles facilitate DOX entering into tumor cells. In tumor-bearing animals, DOX-bubbles + US could provide 3.7-fold suppression of tumor growth compared with the group without insonation (1.8 ± 0.9 cm<sup>3</sup> vs. 8.5 ± 2.2 cm<sup>3</sup>) because of the acceleration of DOX-induced tumor necrosis. In the meantime, the tumor perfusion and volume can be monitored by DOX-bubbles with contrast-enhanced ultrasound imaging. Our data provide useful information in support of translating the use of theranostic US-responsive bubbles for regulated tumor drug delivery into clinical use.https://www.mdpi.com/1999-4923/11/5/223microbubblescontrast-enhanced ultrasoundosteosarcomaenhanced permeabilitydrug-loadedultrasound contrast agentstherasostics |
| spellingShingle | Tai-Tzung Kuo Chung-Hsin Wang Jir-You Wang Hong-Jen Chiou Ching-Hsiang Fan Chih-Kuang Yeh Concurrent Osteosarcoma Theranostic Strategy Using Contrast-Enhanced Ultrasound and Drug-Loaded Bubbles Pharmaceutics microbubbles contrast-enhanced ultrasound osteosarcoma enhanced permeability drug-loaded ultrasound contrast agents therasostics |
| title | Concurrent Osteosarcoma Theranostic Strategy Using Contrast-Enhanced Ultrasound and Drug-Loaded Bubbles |
| title_full | Concurrent Osteosarcoma Theranostic Strategy Using Contrast-Enhanced Ultrasound and Drug-Loaded Bubbles |
| title_fullStr | Concurrent Osteosarcoma Theranostic Strategy Using Contrast-Enhanced Ultrasound and Drug-Loaded Bubbles |
| title_full_unstemmed | Concurrent Osteosarcoma Theranostic Strategy Using Contrast-Enhanced Ultrasound and Drug-Loaded Bubbles |
| title_short | Concurrent Osteosarcoma Theranostic Strategy Using Contrast-Enhanced Ultrasound and Drug-Loaded Bubbles |
| title_sort | concurrent osteosarcoma theranostic strategy using contrast enhanced ultrasound and drug loaded bubbles |
| topic | microbubbles contrast-enhanced ultrasound osteosarcoma enhanced permeability drug-loaded ultrasound contrast agents therasostics |
| url | https://www.mdpi.com/1999-4923/11/5/223 |
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