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The Preparation of Chicken Ex Ovo Embryos and Chorioallantoic Membrane Vessels as In Vivo Model for Contrast-Enhanced Ultrasound Imaging and Microbubble-Mediated Drug Delivery Studies
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Concurrent Osteosarcoma Theranostic Strategy Using Contrast-Enhanced Ultrasound and Drug-Loaded Bubbles

Tai-Tzung Kuo1,2, Chung-Hsin Wang3, Jir-You Wang4,5,6

  • 1Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan. 4348@mmh.org.tw.

Pharmaceutics
|May 11, 2019
PubMed

Insights

This study shows that doxorubicin-loaded microbubbles combined with ultrasound effectively deliver chemotherapy drugs to osteosarcoma tumors. This approach significantly suppresses tumor growth and allows for monitoring via ultrasound imaging.

Area of Science:

  • Biomedical Engineering
  • Oncology
  • Nanotechnology

Background:

  • Osteosarcoma (OS) is a common pediatric bone cancer with significant multidrug resistance.
  • Conventional chemotherapy faces challenges in achieving effective drug doses in tumors without systemic toxicity.

Purpose of the Study:

  • To investigate doxorubicin (DOX)-loaded microbubbles (DOX-bubbles) as carriers for enhanced tumor drug delivery using ultrasound (US).
  • To evaluate the efficacy of DOX-bubbles combined with US in treating osteosarcoma in vitro and in vivo.

Main Methods:

  • Development of DOX-bubbles with high drug payload capacity.
  • In vitro assessment of DOX uptake into tumor cells mediated by DOX-bubbles and 1-MHz US.
  • In vivo evaluation of tumor growth suppression, necrosis, and perfusion monitoring in tumor-bearing animals using DOX-bubbles and US.

Main Results:

  • DOX-bubbles demonstrated high doxorubicin payload efficiency (69.4 ± 9.1%) and concentration (1.4 mg/mL).
  • US-mediated DOX-bubble treatment significantly increased DOX entry into osteosarcoma cells in vitro.
  • In vivo studies showed a 3.7-fold greater suppression of tumor growth with DOX-bubbles + US compared to controls, attributed to accelerated DOX-induced necrosis.
  • DOX-bubbles facilitated contrast-enhanced ultrasound imaging for monitoring tumor perfusion and volume.

Conclusions:

  • DOX-bubbles serve as effective drug carriers for ultrasound-triggered drug delivery in osteosarcoma.
  • The combination of DOX-bubbles and US offers a promising theranostic approach for targeted cancer therapy.
  • This strategy supports the potential translation of US-responsive microbubbles for regulated tumor drug delivery into clinical applications.
Keywords:
contrast-enhanced ultrasounddrug-loadedenhanced permeabilitymicrobubblesosteosarcomatherasosticsultrasound contrast agents

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