Estimating the Delivery Efficiency of Drug-Loaded Microbubbles in Cancer Cells with Ultrasound and Bioluminescence Imaging

Ai Ho Liao, Ying Kai Li, Wei Jiunn Lee, Ming Fang Wu, Hao Li Liu, Min Liang Kuo

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The application of drug-loaded microbubbles (MBs) in combination with ultrasound (US), which results in an increase in capillary permeability at the site of US-sonication-induced MB destruction, may be an efficient method of localized drug delivery. This study investigated the mechanism underlying the US-mediated release of luciferin-loaded MBs through the blood vessels to targeted cells using an in vivo bioluminescence imaging (BLI) system. The luciferin-loaded MBs comprised an albumin shell with a diameter of 1234 ± 394 nm (mean ± SD) and contained 2.48 × 109 bubbles/mL; within each MB, the concentration of encapsulated luciferin was 1.48 × 10-10 mg/bubble. The loading efficiency of luciferin in MBs was only about 19.8%, while maintaining both the bioluminescence and acoustic properties. In vitro and in vivo BLI experiments were performed to evaluate the US-mediated release of luciferin-loaded MBs. For in vitro results, the increase in light emission of luciferin-loaded albumin-shelled MBs after destruction via US sonication (6.24 ± 0.72 × 107 photons/s) was significantly higher than that in the luciferin-loaded albumin-shelled MBs (3.11 ± 0.33 × 107 photons/s) (p <0.05). The efficiency of the US-mediated release of luciferin-loaded MBs in 4T1-luc2 tumor-bearing mice was also estimated. The signal intensity of the tumor with US destruction at 3 W/cm2 for 30 s was significantly higher than without US destruction at 3 (p = 0.025), 5 (p = 0.013), 7 (p = 0.012) and 10 (p = 0.032) min after injecting luciferin-loaded albumin-shelled MBs. The delivery efficiency was, thus, improved with US-mediated release, allowing reduction of the total injection dose of luciferin.

Original languageEnglish
Pages (from-to)1938-1948
Number of pages11
JournalUltrasound in Medicine and Biology
Volume38
Issue number11
DOIs
Publication statusPublished - Nov 2012
Externally publishedYes

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Keywords

  • High-frequency ultrasound
  • In vivo bioluminescence imaging system
  • Luciferase-expressing breast cancer cell
  • Luciferin-loaded microbubbles

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology
  • Biophysics

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