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Combined image guided monitoring the pharmacokinetics of rapamycin loaded human serum albumin nanoparticles with a split luciferase reporter
Wang, Fu1,2; Yang, Kai2,3,4,5; Wang, Zhe2; Ma, Ying2; Gutkind, J. Silvio6; Hida, Naoki2; Niu, Gang2; Tian, Jie1,7
2016
发表期刊NANOSCALE
卷号8期号:7页码:3991-4000
文章类型Article
摘要Imaging guided techniques have been increasingly employed to investigate the pharmacokinetics (PK) and biodistribution of nanoparticle based drug delivery systems. In most cases, however, the PK profiles of drugs could vary significantly from those of drug delivery carriers upon administration in the blood circulation, which complicates the interpretation of image findings. Herein we applied a genetically encoded luciferase reporter in conjunction with near infrared (NIR) fluorophores to investigate the respective PK profiles of a drug and its carrier in a biodegradable drug delivery system. In this system, a prototype hydrophobic agent, rapamycin (Rapa), was encapsulated into human serum albumin (HSA) to form HSA Rapa nanoparticles, which were then labeled with Cy5 fluorophore to facilitate the fluorescence imaging of HSA carrier. Meanwhile, we employed transgenetic HN12 cells that were modified with a split luciferase reporter, whose bioluminescence function is regulated by Rapa, to reflect the PK profile of the encapsulated agent. It was interesting to discover that there existed an obvious inconsistency of PK behaviors between HSA carrier and rapamycin in vitro and in vivo through near infrared fluorescence imaging (NIFRI) and bioluminescence imaging (BLI) after treatment with Cy5 labeled HSA Rapa. Nevertheless, HSA Rapa nanoparticles manifested favorable in vivo PK and tumor suppression efficacy in a follow-up therapeutic study. The developed strategy of combining a molecular reporter and a fluorophore in this study could be extended to other drug delivery systems to provide profound insights for non-invasive real-time evaluation of PK profiles of drug-loaded nanoparticles in pre-clinical studies.
关键词Split Luciferasereporter Humanserum Albumin Nanoparticles Rapamycin
WOS标题词Science & Technology ; Physical Sciences ; Technology
DOI10.1039/c5nr07308a
关键词[WOS]MAMMALIAN TARGET ; SIGNALING PATHWAY ; CANCER-THERAPY ; DRUG-DELIVERY ; CELLS ; INHIBITION ; METABOLISM ; PACLITAXEL ; SYSTEMS ; CARRIER
收录类别SCI
语种英语
项目资助者National Basic Research and Development Program of China (973 Program)(2013CB733803) ; National Natural Science Foundation of China(81571721 ; Intramural Research Program, National Institute of Biomedical Imaging and Bioengineering (NIBIB) ; National Institutes of Health (NIH) ; 81301214)
WOS研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
WOS类目Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary ; Physics, Applied
WOS记录号WOS:000370761700017
引用统计
被引频次:8[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.ia.ac.cn/handle/173211/11348
专题中国科学院分子影像重点实验室
通讯作者Tian, Jie
作者单位1.Xidian Univ, Engn Res Ctr Mol & Neuro Imaging, Sch Life Sci & Technol, Minist Educ, Xian 710071, Shaanxi, Peoples R China
2.Natl Inst Biomed Imaging & Bioeng, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA
3.Soochow Univ, Coll Med, Collaborat Innovat Ctr Suzhou Nano Sci & Technol, Sch Radiat Med & Protect, Suzhou 215123, Jiangsu, Peoples R China
4.Soochow Univ, Coll Med, Collaborat Innovat Ctr Suzhou Nano Sci & Technol, Sch Radiol & Interdisciplinary Sci RAD X, Suzhou 215123, Jiangsu, Peoples R China
5.Soochow Univ, Coll Med, Collaborat Innovat Ctr Radiat Med, Jiangsu Higher Educ Inst, Suzhou 215123, Jiangsu, Peoples R China
6.Natl Inst Craniofacial & Dent Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA
7.Chinese Acad Sci, Inst Automat, Key Lab Mol Imaging, Beijing 100190, Peoples R China
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GB/T 7714
Wang, Fu,Yang, Kai,Wang, Zhe,et al. Combined image guided monitoring the pharmacokinetics of rapamycin loaded human serum albumin nanoparticles with a split luciferase reporter[J]. NANOSCALE,2016,8(7):3991-4000.
APA Wang, Fu.,Yang, Kai.,Wang, Zhe.,Ma, Ying.,Gutkind, J. Silvio.,...&Tian, Jie.(2016).Combined image guided monitoring the pharmacokinetics of rapamycin loaded human serum albumin nanoparticles with a split luciferase reporter.NANOSCALE,8(7),3991-4000.
MLA Wang, Fu,et al."Combined image guided monitoring the pharmacokinetics of rapamycin loaded human serum albumin nanoparticles with a split luciferase reporter".NANOSCALE 8.7(2016):3991-4000.
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