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作 者:TREVOR D.MCKEE JUAN CHEN IAN CORBIN GANG ZHENG RAMA KHOKHA
机构地区:[1]Ontario Cancer Institute University Health Network,Toronto,Ontario [2]STTARR Innovation Center University Health Network,Toronto,Canada [3]Department of Medical Biophysics University of Toronto,Toronto,Canada [4]Advanced Imaging Research Center University of Texas Southwestern Medical Center at Dallas Dallas,USA
出 处:《Journal of Innovative Optical Health Sciences》2012年第4期8-17,共10页创新光学健康科学杂志(英文)
基 金:supported by a Department of Defense Breast Cancer Research Program Idea Award,the Susan G.Komen Foundation,Princess Margaret Hospital Foundation,Canadian Institute of Health Research,and Joey and Toby Tanen-baum/Brazilian Ball Chair in Prostate Cancer Research,University Health Network.
摘 要:We have developed a noninv asive imaging method to quantify in viwo drug delivery pharmaco-kinetics without the need for blood or tissue collection to determine drug concentration.By combining the techniques of hy perspectral imaging and a dorsal skinfold window chamber,this method enabled the real-time monitoring of vascular transport and tissue deposition of nano-particles 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>12h).These HDL nanoparticles could eficiently carry cargo DiR-BOA to extravasate from blood vesels,difuse through extr acellular 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 inhi bition with excess EGFR specifc 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 eficiency,providing a dynamic window into the devel opment and application of novel drug delivery systems.
关 键 词:SPECIFICITY kinetics COMPETITIVE
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