QUANTIFYING NANOPARTICLE TRANSPORT IN VIVO USING HYPERSPECTRAL IMAGING WITH A DORSAL SKINFOLD WINDOW CHAMBER.
QUANTIFYING NANOPARTICLE TRANSPORT IN VIVO USING HYPERSPECTRAL IMAGING WITH A DORSAL SKINFOLD WINDOW CHAMBER.
复制标题
DOI：
10.1142/s179354581250023x
复制
发表时间：
2012-12
影响因子：
2.5
通讯作者：
T. McKee;Juan Chen;I. Corbin;G. Zheng;R. Khokha
中科院分区：
文献类型：
--
作者：
T. McKee;Juan Chen;I. Corbin;G. Zheng;R. Khokha
我们已经开发了一种非侵入性成像方法来量化体内药物递送药代动力学，而不需要血液或组织收集来确定药物浓度。通过结合高光谱成像技术和背部皮褶窗口室，该方法能够实时监测近红外（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，我们定量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，并渗透和保留在肿瘤部位。EGFR靶向的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可视化。总之，这种成像技术可能有助于为临床前药物的新型基于成像的药代动力学测定和药物递送效率的评价指明方向，为新型药物递送系统的开发和应用提供动态窗口。
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.