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QUANTIFYING NANOPARTICLE TRANSPORTIN VIVOUSING HYPERSPECTRAL IMAGING WITH A DORSAL SKINFOLD WINDOW CHAMBER
Journal of Innovative Optical Health Sciences ( IF 2.5 ) Pub Date : 2012-08-06 , DOI: 10.1142/s179354581250023x
Trevor D McKee 1, 2 , Juan Chen 1 , Ian Corbin 1, 3 , Gang Zheng 1, 4 , Rama Khokha 1, 4
Affiliation  

We have developed a noninvasive imaging method to quantify in vivo drug delivery pharmacokinetics without the need for blood or tissue collection to determine drug concentration. By combining the techniques of hyperspectral imaging and a dorsal skinfold window chamber, this method enabled the real-time monitoring of vascular transport and tissue deposition of nanoparticles labeled with near-infrared (NIR) dye. Using this imaging method, we quantified the delivery pharmacokinetics of the native high-density lipoprotein (HDL) and epidermal growth factor receptor (EGFR)-targeted HDL nanoparticles and demonstrated these HDLs had long circulation time in blood stream (half-life >12 h). These HDL nanoparticles could efficiently carry cargo DiR-BOA to extravasate from blood vessels, diffuse through extracellular matrix, and penetrate and be retained in the tumor site. The EGFR targeting specificity of EGFR-targeted HDL (EGFR-specific peptide conjugated HDL) was also visualized in vivo by competitive inhibition with excess EGFR-specific peptide. In summary, this imaging technology may help point the way toward the development of novel imaging-based pharmacokinetic assays for preclinical drugs and evaluation of drug delivery efficiency, providing a dynamic window into the development and application of novel drug delivery systems.

中文翻译:

用背侧皮褶窗室量化高光谱成像中的纳米粒子转运

我们开发了一种无创成像方法来量化体内药物递送的药代动力学,而无需采集血液或组织来确定药物浓度。通过结合高光谱成像技术和背侧皮褶窗室,该方法能够实时监测用近红外 (NIR) 染料标记的纳米颗粒的血管运输和组织沉积。使用这种成像方法,我们量化了天然高密度脂蛋白 (HDL) 和表皮生长因子受体 (EGFR) 靶向 HDL 纳米颗粒的递送药代动力学,并证明这些 HDL 在血流中具有较长的循环时间(半衰期 > 12 小时) )。这些 HDL 纳米颗粒可以有效地携带货物 DiR-BOA 从血管渗出,通过细胞外基质扩散,并穿透并保留在肿瘤部位。EGFR 靶向 HDL(EGFR 特异性肽缀合的 HDL)的 EGFR 靶向特异性也通过与过量 EGFR 特异性肽的竞争性抑制在体内显现。总之,这种成像技术可能有助于为临床前药物开发新的基于成像的药代动力学分析和药物递送效率评估指明道路,为新型药物递送系统的开发和应用提供动态窗口。
更新日期:2012-08-06
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