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Tumor Cell-Specific Nuclear Targeting of Functionalized Graphene Quantum Dots In Vivo.

Authors
  • Yao, Chenjie1
  • Tu, Yusong2
  • Ding, Lin1
  • Li, Chenchen1
  • Wang, Jiao3
  • Fang, Haiping4
  • Huang, Yanan1
  • Zhang, Kangkang1
  • Lu, Quan5
  • Wu, Minghong1
  • Wang, Yanli1, 5
  • 1 Institute of Nano-chemistry and Nano-biology, Shanghai University , Shanghai 200444, P.R. China. , (China)
  • 2 College of Physics Science and Technology, Yangzhou University , Jiangsu 225009, P.R. China. , (China)
  • 3 School of Life Science, Shanghai University , Shanghai 200444, P.R. China. , (China)
  • 4 Shanghai Institute of Applied Physics, Chinese Academy of Sciences , Shanghai 201800, P. R. China. , (China)
  • 5 Program in Molecular and Integrative Physiological Sciences, Harvard T.H. Chan School of Public Health , Boston, Massachusetts 02115, United States. , (United States)
Type
Published Article
Journal
Bioconjugate Chemistry
Publisher
American Chemical Society
Publication Date
Oct 18, 2017
Volume
28
Issue
10
Pages
2608–2619
Identifiers
DOI: 10.1021/acs.bioconjchem.7b00466
PMID: 28903003
Source
Medline
License
Unknown

Abstract

Specific targeting of tumor tissues is essential for tumor imaging and therapeutics but remains challenging. Here, we report an unprecedented method using synthetic sulfonic-graphene quantum dots (sulfonic-GQDs) to exactly target the cancer cell nuclei in vivo without any bio- ligand modification, with no intervention in cells of normal tissues. The key factor for such selectivity is the high interstitial fluid pressure (IFP) in tumor tissues, which allows the penetration of sulfonic-GQDs into the plasma membrane of tumor cells. In vitro, the sulfonic-GQDs are repelled out of the cell membrane because of the repulsive force between negatively charged sulfonic-GQDs and the cell membranes which contributes to the low distribution in normal tissues in vivo. However, the plasma membrane-crossing process can be activated by incubating cells in ultrathin film culture medium because of the attachment of sulfonic-GQDs on cell memebranes. Molecular dynamics simulations demonstrated that, once transported across the plasma membrane, the negatively charged functional groups of these GQDs will leave the membrane with a self-cleaning function retaining a small enough size to achieve penetration through the nuclear membrane into the nucleus. Our study showed that IFP is a previously unrecognized mechanism for specific targeting of tumor cell nuclei and suggested that sulfonic-GQDs may be developed into novel tools for tumor-specific imaging and therapeutics.

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