Crossing the blood-brain-barrier with transferrin conjugated carbon dots: A zebrafish model study

被引:115
作者
Li, Shanghao [1 ]
Peng, Zhili [1 ]
Dallman, Julia [2 ]
Baker, James [2 ]
Othman, Abdelhameed M. [3 ,4 ]
Blackwelder, Patrica L. [5 ,6 ]
Leblanc, Roger M. [1 ]
机构
[1] Univ Miami, Dept Chem, 1301 Mem Dr, Coral Gables, FL 33146 USA
[2] Univ Miami, Dept Biol, 1301 Mem Dr, Coral Gables, FL 33146 USA
[3] Taibah Univ, Fac Sci Yanbu, Dept Chem, Yanbu, Saudi Arabia
[4] Univ Sadat City, Dept Environm Biotechnol Genet Engn & Biotechnol, Sadat City, Egypt
[5] Univ Miami, Ctr Adv Microscopy & Marine Geosci, 1301 Mem Dr, Coral Gables, FL 33146 USA
[6] Nova Southeastern Univ, Oceanog Ctr, 8000 North Ocean Dr, Dania, FL 33004 USA
基金
美国国家科学基金会;
关键词
Blood-brain-barrier; Carbon dots; Central nervous system; Transferrin; RECEPTOR-MEDIATED ENDOCYTOSIS; DRUG-DELIVERY; NANOPARTICLES; AGGREGATION; NANOPROBES; EMISSION; SYSTEM;
D O I
10.1016/j.colsurfb.2016.05.007
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
Drug delivery to the central nervous system (CNS) in biological systems remains a major medical challenge due to the tight junctions between endothelial cells known as the blood brain barrier (BBB). Here we use a zebrafish model to explore the possibility of using transferrin-conjugated carbon dots (C-Dots) to ferry compounds across the BBB. C-Dots have previously been reported to inhibit protein fibrillation, and they are also used to deliver drugs for disease treatment. In terms of the potential medical application of C-Dots for the treatment of CNS diseases, one of the most formidable challenges is how to deliver them inside the CNS. To achieve this in this study, human transferrin was covalently conjugated to C-Dots. The conjugates were then injected into the vasculature of zebrafish to examine the possibility of crossing the BBB in vivo via transferrin receptor-mediated endocytosis. The experimental observations suggest that the transferrin-C-Dots can enter the CNS while C-Dots alone cannot. (C) 2016 Elsevier B.V. All rights reserved.
引用
收藏
页码:251 / 256
页数:6
相关论文
共 43 条
[1]   Astrocyte-endothelial interactions at the blood-brain barrier [J].
Abbott, NJ ;
Rönnbäck, L ;
Hansson, E .
NATURE REVIEWS NEUROSCIENCE, 2006, 7 (01) :41-53
[2]   Zebrafish Bone and General Physiology Are Differently Affected by Hormones or Changes in Gravity [J].
Aceto, Jessica ;
Nourizadeh-Lillabadi, Rasoul ;
Maree, Raphael ;
Dardenne, Nadia ;
Jeanray, Nathalie ;
Wehenkel, Louis ;
Alestrom, Peter ;
van Loon, Jack J. W. A. ;
Muller, Marc .
PLOS ONE, 2015, 10 (06)
[3]   Site-directed nanoparticle labeling of cytochrome c [J].
Aubin-Tam, Marie-Eve ;
Hwang, Wonmuk ;
Hamad-Schifferli, Kimberly .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (11) :4095-4100
[4]   JUNCTIONS BETWEEN INTIMATELY APPOSED CELL MEMBRANES IN VERTEBRATE BRAIN [J].
BRIGHTMA.MW ;
REESE, TS .
JOURNAL OF CELL BIOLOGY, 1969, 40 (03) :648-+
[5]   Targeted In Vivo Imaging of Microscopic Tumors with Ferritin- based Nanoprobes Across Biological Barriers [J].
Cao, Changqian ;
Wang, Xuxia ;
Cai, Yao ;
Sun, Lei ;
Tian, Lanxiang ;
Wu, Hao ;
He, Xiaoqing ;
Lei, Hao ;
Liu, Weifeng ;
Chen, Guanjun ;
Zhu, Rixiang ;
Pan, Yongxin .
ADVANCED MATERIALS, 2014, 26 (16) :2566-2571
[6]   Zebrafish cerebrospinal fluid mediates cell survival through a retinoid signaling pathway [J].
Chang, Jessica T. ;
Lehtinen, Maria K. ;
Sive, Hazel .
DEVELOPMENTAL NEUROBIOLOGY, 2016, 76 (01) :75-92
[7]   Protein misfolding, functional amyloid, and human disease [J].
Chiti, Fabrizio ;
Dobson, Christopher M. .
ANNUAL REVIEW OF BIOCHEMISTRY, 2006, 75 :333-366
[8]   The transferrin receptor part II: Targeted delivery of therapeutic agents into cancer cells [J].
Daniels, Tracy R. ;
Delgado, Tracie ;
Helguera, Gustavo ;
Penichet, Manuel L. .
CLINICAL IMMUNOLOGY, 2006, 121 (02) :159-176
[9]   Transferrin receptor-targeted theranostic gold nanoparticles for photosensitizer delivery in brain tumors [J].
Dixit, Suraj ;
Novak, Thomas ;
Miller, Kayla ;
Zhu, Yun ;
Kenney, Malcolm E. ;
Broome, Ann-Marie .
NANOSCALE, 2015, 7 (05) :1782-1790
[10]   Regulation and function of Dbx genes in the zebrafish spinal cord [J].
Gribble, Suzanna L. ;
Nikolaus, O. Brant ;
Dorsky, Richard I. .
DEVELOPMENTAL DYNAMICS, 2007, 236 (12) :3472-3483