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Open AccessArticle

Concurrent Osteosarcoma Theranostic Strategy Using Contrast-Enhanced Ultrasound and Drug-Loaded Bubbles

1
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan
2
Department of Neurosurgery, Hsin-chu Mackay Memorial Hospital, Hsinchu 30071, Taiwan
3
Department of Orthopaedics and Traumatology, Taipei Veterans General Hospital, Taipei 11217, Taiwan
4
Department of Orthopaedics, Therapeutical and Research Center of Musculoskeletal Tumor, Taipei Veterans General Hospital, Taipei 11217, Taiwan
5
Institute of Traditional Medicine. National Yang-Ming University, Taipei 11221, Taiwan
6
Department of Radiology, Taipei-Veterans General Hospital, Taipei 11217, Taiwan
7
Institute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu 30013, Taiwan
*
Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(5), 223; https://doi.org/10.3390/pharmaceutics11050223
Received: 1 April 2019 / Revised: 1 May 2019 / Accepted: 6 May 2019 / Published: 8 May 2019
(This article belongs to the Special Issue Micro/Nano-Bubbles as a New Ultrasound Imaging and Drug Delivery Tool)
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 cm3 vs. 8.5 ± 2.2 cm3) 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. View Full-Text
Keywords: microbubbles; contrast-enhanced ultrasound; osteosarcoma; enhanced permeability; drug-loaded; ultrasound contrast agents; therasostics microbubbles; contrast-enhanced ultrasound; osteosarcoma; enhanced permeability; drug-loaded; ultrasound contrast agents; therasostics
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Kuo, T.-T.; Wang, C.-H.; Wang, J.-Y.; Chiou, H.-J.; Fan, C.-H.; Yeh, C.-K. Concurrent Osteosarcoma Theranostic Strategy Using Contrast-Enhanced Ultrasound and Drug-Loaded Bubbles. Pharmaceutics 2019, 11, 223.

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