title: Estimating the delivery efficiency of drug-loaded microbubbles in cancer cells with ultrasound and bioluminescence imaging.
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.
authors.affiliation: Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan. aiho@mail.ntust.edu.tw
authors.forename: Ai-Ho
authors.initials: AH
authors.lastname: Liao
authors.forename: Ying-Kai
authors.initials: YK
authors.lastname: Li
authors.forename: Wei-Jiunn
authors.initials: WJ
authors.lastname: Lee
authors.forename: Ming-Fang
authors.initials: MF
authors.lastname: Wu
authors.forename: Hao-Li
authors.initials: HL
authors.lastname: Liu
authors.forename: Min-Liang
authors.initials: ML
authors.lastname: Kuo
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods; D018274:Electroporation / Q000379:methods; D005260:Female; D008163:Luminescent Measurements / Q000379:methods*; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice; D045423:Microbubbles / Q000627:therapeutic use; D057054:Molecular Imaging / Q000379:methods*; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014463:Ultrasonography / Q000379:methods*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel