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Quantifying nanoparticle transport in vivo using hyperspectral imaging with a dorsal skinfold window chamber

机译:使用高光谱成像和背部皮褶窗腔室对体内纳米颗粒的运输进行定量

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摘要

We have developed a noninvasive imaging method to quantify in vivo drug delivery pharmaco-kinetics 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.
机译:我们已经开发出了一种无创成像方法,可以定量体内药物传递的药代动力学,而无需收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部皮褶窗腔室技术,该方法可以实时监测血管注射和近红外(NIR)染料标记的纳米颗粒的组织沉积。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)靶向的HDL纳米颗粒的递送药代动力学,并证明了这些HDL在血液中的循环时间长(半衰期> 12 h )。这些HDL纳米颗粒可以有效地携带货物DiR-BOA从血管中渗出,通过细胞外基质扩散,并渗透并保留在肿瘤部位。 EGFR靶向的HDL(EGFR特异性肽结合的HDL)的EGFR靶向特异性也通过体内与过量EGFR特异性肽的竞争性抑制而显现出来。总之,这种成像技术可能有助于为临床前药物的基于成像的新型药代动力学测定方法的开发和药物输送效率的评估指明方向,为新型药物输送系统的开发和应用提供了动态窗口。

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