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Transthyretin as a new transporter of nanoparticles for receptor-mediated transcytosis in rat brain microvessels

Transthyretin as a new transporter of nanoparticles for receptor-mediated transcytosis in rat brain microvessels
Kim, So YeunChoi, Eun-SookLee, Hyo-JungMoon, CheilKim, Eunjoo
DGIST Authors
Moon, CheilKim, Eunjoo
Issue Date
Colloids and Surfaces B: Biointerfaces, 136, 989-996
Article Type
AnimalAnimal CellAnimal ExperimentAnimal TissueAnimalsAssaysBiological TransportBloodBlood-Brain BarrierBlood-Brain Barrier (BBB)Blood Brain BarrierBrainBrain Capillary Endothelial CellCell CultureCells, CulturedClathrin-Dependent EndocytosisConfocal MicroscopyControlled StudyCreatine Kinase MMDirected TransportDrug DeliveryEndothelial CellsHumanHuman CellIn-Vitro AssaysIn Vitro StudyIn Vivo StudyMALDI-TOF Mass SpectroscopyMaleMass SpectrometryMatrix Assisted Laser Desorption Ionization Time of Flight Mass SpectrometryMedical NanotechnologyMetabolismMicroscopy, ConfocalMicrovasculatureMicrovesselsMolecular BiologyNanomedicineNanoparticleNanoparticlesNon-HumanPhysiologyPrealbuminPriority JournalProteinsQuantum DotQuantum Dot NanoparticlesRatRatsRats, Sprague-DawleyReceptor-Mediated TranscytosisSemiconductor Quantum DotsSprague Dawley RatTissue DistributionTranscytosisTransport At The Cellular LevelTransthyretinValidation StudyVascularization
Many drugs are unable to breach the blood-brain barrier (BBB). Protein-directed transport of nanomedicine by receptor-mediated transcytosis (RMT) has been investigated as a means to overcome this problem. In this study, we screened transporters using an in vitro transcytosis assay system in rat serum to identify candidates that could guide nanoparticles through the BBB by RMT. The proteins that showed over 5-fold decreases in RMT when treated with chloropromazine, an inhibitor of clathrin-dependent endocytosis, were selected and identified by Maldi-TOF mass spectroscopy. Eleven proteins, including transthyretin (Ttr), and creatine kinase-muscle type (CKM), were identified as being capable of penetrating the endothelial cell layer by RMT. Among them, 10 proteins have not yet been used to transport nanomaterials across the BBB. To validate their activity as nanoparticle transporters in vivo, Ttr and CKM were conjugated to the surface of quantum dot (QD) nanoparticles and administrated intravenously. After 8. h, the distribution of Ttr-QDs and CKM-QDs in brain tissue was analyzed. The results showed transcytosis of Ttr-QD conjugates across the BBB in rats as well as in in vitro assays, which was in contrast to the results observed for bare QDs and CKM-QDs. Taken together, these results indicate that Ttr is a new putative transporter for nanomedicines across the BBB. © 2015 Elsevier B.V.
Elsevier B.V.
Related Researcher
  • Author Kim, Eunjoo  
  • Research Interests Biomarker, liquid biopsy, nanomedicine, molecular diagnosis
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Department of Brain and Cognitive SciencesMoon Lab1. Journal Articles
Companion Diagnostics and Medical Technology Research Group1. Journal Articles

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