Investigation of Nanoparticle Accumulation in Tumor Tissues Enhanced by Focused Ultrasound with Microbubbles
Date Issued
2010
Date
2010
Author(s)
Lin, Chung-Yin
Abstract
Ultrasound-enhanced drug delivery system is a promising technique for noninvasive cancer treatment. 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 uL/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 uL of the LQD solution after the sonication. The mice were sacrificed about 24 hr 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 (ug Cd)/(g tumor) for 30, 80, 130, and 180 nm of LQDs, respectively; compared to 1.12, 0.75, 0.26, and 0.34 (ug 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.
Furthermore, we studied the effects of the injected UCA dose (0-300 uL/kg), FUS sonication duration (0-300 sec), and treatment-procedure sequence on the accumulation of nanoparticles in the tumors 24 hr after the treatment, and the time response of the accumulation (0.5-24 hr). After the treatment, the mice were sacrificed and perfused, and then the tumor tissues were harvested for quantifying the amount of nanoparticles using graphite furnace atomic absorption spectrometry (GF-AAS). The results showed that pulsed-FUS sonication with UCA can effectively enhance the vascular permeability for LQD nanoparticle delivery into the sonicated tumors. It indicates that this technique is promising for a better nanodrug delivery for tumor chemotherapy.
Subjects
Focused ultrasound (FUS)
Ultrasound contrast agent (UCA)
Microbubbles
Lipid-coated quantum dots
Enhanced nanoparticle delivery
SDGs
Type
thesis
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