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

Intracellular delivery and ultrasonic activation of folate receptor-targeted phase-change contrast agents in breast cancer cells in vitro.
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DOI:
10.1016/j.jconrel.2016.09.010
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发表时间:
2016-12-10
期刊:
Journal of controlled release : official journal of the Controlled Release Society
影响因子:
--
通讯作者:
Matsunaga TO
Matsunaga TO
中科院分区:
其他
文献类型:
--
作者:
Marshalek JP;Sheeran PS;Ingram P;Dayton PA;Witte RS;Matsunaga TO

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乳腺癌是一种多样而复杂的疾病,仍然是妇女死亡的主要原因之一。需要新颖、创新的成像和治疗方法来补充现有的技术。在这项研究中,我们在体外MDA-MB-231和MCF-7乳腺癌细胞中提供了叶酸受体(FR)靶向相变造影剂(PCCAs)的细胞内递送和超声刺激激活的证据。pcca是一种脂质包被、全氟化碳填充的颗粒,其配方为纳米级液滴,能够蒸发成气体微泡,用于成像或治疗。细胞与1:1的十氟丁烷(DFB) /八氟丙烷(OFP) pcca孵育1小时,通过共聚焦显微镜成像,暴露于超声(9 MHz, MI = 1.0或1.5),超声后再次成像。两种细胞系均在细胞内观察到fr靶向的pcca,但MDA-MB-231细胞的摄取率(MI = 1.0时为93.0%,MI = 1.5时为79.5%)明显高于MCF-7细胞(MI = 1.0时为42.4%,MI = 1.5时为35.7%)。与非靶向PCCA相比,叶酸掺入使MDA-MB-231细胞的细胞内PCCA检测频率增加了45倍,MCF-7细胞的细胞内PCCA检测频率增加了7倍。胞内活化的PCCAs范围为500 nm ~ 6微米(IQR = 800 nm ~ 1.5微米),平均直径为1.15±0.59 (SD)微米。本文提出的工作证明了使用乳腺癌细胞进行PCCA细胞内传递和激活的可行性,为细胞内成像或超声治疗传递提供了新的平台。
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 hour, 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 intracellularly 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 microns (IQR = 800 nm – 1.5 microns) 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.
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