Effects of Focused Ultrasound and Microbubbles on the Vascular Permeability of Nanoparticles Delivered into Mouse Tumors

Lin, Chung-Yin; Huang, Yen-Lin; Li, Jia-Rong; Chang, Fu-Hsiung; Lin, Win-Li

doi:10.1016/j.ultrasmedbio.2010.06.003

« Previous Next »Ultrasound in Medicine and Biology
Volume 36, Issue 9 , Pages 1460-1469, September 2010

Effects of Focused Ultrasound and Microbubbles on the Vascular Permeability of Nanoparticles Delivered into Mouse Tumors

Chung-Yin Lin
- Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan
- Division of Medical Engineering Research, National Health Research Institutes, Miaoli, Taiwan
Yen-Lin Huang
- Department of Nephrology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
Jia-Rong Li
- Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan
Fu-Hsiung Chang
- Institute of Molecular and Biochemistry, College of Medicine, National Taiwan University, Taipei, Taiwan
Win-Li Lin
- Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan
- Division of Medical Engineering Research, National Health Research Institutes, Miaoli, Taiwan
- Address correspondence to: Win-Li Lin, Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Sec. 1, Jen-Ai Road, Taipei 100, Taiwan.

Received 21 December 2009; received in revised form 8 May 2010; accepted 8 June 2010.

Abstract

Ultrasound sonication with microbubbles (MBs) was evaluated for enhancement of the release of nanoparticles from vasculature to tumor tissues. In this study, tumor-bearing Balb/c mice were insonicated with focused ultrasound (FUS) in the tumors after the injection of MBs (SonoVue^®) and then lipid-coated quantum dot (LQD) nanoparticles (130 ± 25 nm) were injected through the tail vein. We studied the effects of the injected MB dose (0–300 μL/kg), sonication duration (0–300 s) and treatment-procedure sequence on the accumulation of nanoparticles in the tumors 24 h after the treatment and the time response of the accumulation (0.5–24 h). 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 MBs 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. (E-mail: winli@ntu.edu.tw)

Key Words: Focused ultrasound (FUS), Microbubbles (MBs), Nanoparticles, Tumor tissues, Delivery enhancement