Intracellular delivery and ultrasonic activation of folate receptor-targeted phase-change contrast agents in breast cancer cells in vitro

JOURNAL OF CONTROLLED RELEASE

卷:243

Article

Marshalek, Joseph P.¹  Sheeran, Paul S.^2,3  Ingram, Pier¹  Dayton, Paul A.^4,5  Witte, Russell S.¹  Matsunaga, Terry O.¹ 

[1] Univ Arizona, Dept Med Imaging, Tucson, AZ 85721 USA

[2] Sunnybrook Res Inst, Dept Phys Sci, Toronto, ON, Canada

[3] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada

[4] Univ N Carolina, Joint Dept Biomed Engn, Chapel Hill, NC USA

[5] North Carolina State Univ, Chapel Hill, NC USA

关键词: Ultrasound;    Phase-change contrast agent;    Microbubble;    Nanodroplet;    Perfluorocarbon;    Decafluorobutane;    Octafluoropropane;    Folate receptor;    Breast cancer;   

DOI  :  10.1016/j.jconrel.2016.09.010

来源: Elsevier

【 摘 要 】

Breast cancer is a diverse and complex disease that remains one of the leading causes of death among women. Novel, outside-of-the-box imaging and treatment methods are needed to supplement currently available technologies. In this study, we present evidence for the intracellular delivery and ultrasound-stimulated activation of folate receptor (FR)-targeted phase-change contrast agents (PCCAs) in MDA-MB-231 and MCF-7 breast cancer cells in vitro. PCCAs are lipid-coated, perfluorocarbon-filled particles formulated as nanoscale liquid droplets capable of vaporization into gaseous microbubbles for imaging or therapy. Cells were incubated with 1:1 decafluorobutane (DFB)/octafluoropropane (OFP) PCCAs for 1 h, imaged via confocal microscopy, exposed to ultrasound (9 MHz, MI = 1.0 or 1.5), and imaged again after insonation. FR-targeted PCCAs were observed intra-cellularly in both cell lines, but uptake was significantly greater (p < 0.001) in MDA-MB-231 cells (93.0% internalization at MI = 1.0, 79.5% at MI = 1.5) than MCF-7 cells (42.4% internalization at MI = 1.0, 35.7% at MI = 1.5). Folate incorporation increased the frequency of intracellular PCCA detection 45-fold for MDA-MB-231 cells and 7-fold for MCF-7 cells, relative to untargeted PCCAs. Intracellularly activated PCCAs ranged from 500 nm to 6 mu m (IQR = 800 nm-1.5 mu m) with a mean diameter of 1.15 +/- 0.59 (SD) microns. The work presented herein demonstrates the feasibility of PCCA intracellular delivery and activation using breast cancer cells, illuminating a new platform toward intracellular imaging or therapeutic delivery with ultrasound. (C) 2016 Elsevier B.V. All rights reserved.

【 授权许可】

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