Quantitative and qualitative investigation into the impact of focused ultrasound with microbubbles on the triggered release of nanoparticles from vasculature in mouse tumors.
Ultrasound-mediated microbubble destruction may enhance the release of nanoparticles from vasculature to tumor tissues. In this study, we used four different sizes of lipid-coated CdSe quantum dot (LQD) nanoparticles ranging from 30 to 180 nm, 1.0-MHz pulsed focused ultrasound (FUS) with a peak acoustic pressure of 1.2-MPa, and an ultrasound contrast agent (UCA; SonoVue) at a dose of 30 microL/kg to investigate any enhancement of targeted delivery. Tumor-bearing male Balb/c mice were first injected with UCA intravenously, were then sonicated at the tumors with FUS, and were finally injected with 50 microL of the LQD solution after the sonication. The mice were sacrificed about 24h after the sonication, and then we quantitatively and qualitatively evaluated the deposition of LQDs in the tumors by using graphite furnace atomic absorption spectrometry (GF-AAS), photoluminescence spectrometry (PL), and harmonic generation microscopy (HGM). Further, immunoblotting analysis served to identify the biochemical markers reflecting the vascular rupture. The experimental results show that the amount of LQDs deposited in tumor tissues was greater in cases of FUS/UCA application, especially for smaller LQDs, being 4.47, 2.27, 0.99, and 0.82 (microg Cd)/(g tumor) for 30, 80, 130, and 180 nm of LQDs, respectively; compared to 1.12, 0.75, 0.26, and 0.34 (microg Cd)/(g tumor) in absence of FUS/UCA. The immunoblotting analysis further indicates that FUS-induced UCA oscillation/destruction results in rupture areas in blood vessels increasing the vascular permeability and thus justifying for the higher quantity of nanoparticles deposited in tumors.
Lin
Chung-Yin
CY
Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan; Division of Medical Engineering Research, National Health Research Institutes, Miaoli, Taiwan.
Liu
Tzu-Ming
TM
Chen
Chao-Yu
CY
Huang
Yen-Lin
YL
Huang
Wei-Kai
WK
Sun
Chi-Kuang
CK
Chang
Fu-Hsiung
FH
Lin
Win-Li
WL
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D019187:Cadmium Compounds / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D008055:Lipids / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D045423:Microbubbles; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009369:Neoplasms / Q000098:blood supply / Q000378:metabolism*; D019007:P-Selectin / Q000378:metabolism; D010743:Phospholipids / Q000008:administration & dosage; D045663:Quantum Dots; D018036:Selenium Compounds / Q000008:administration & dosage / Q000737:chemistry; D013010:Sonication; D013459:Sulfur Hexafluoride / Q000008:administration & dosage; D014465:Ultrasonics
D019187:Cadmium Compounds; D008055:Lipids; D019007:P-Selectin; D010743:Phospholipids; D018036:Selenium Compounds; C420843:contrast agent BR1; C058667:cadmium selenide; D013459:Sulfur Hexafluoride