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Supramolecularly Engineered Circular Bivalent Aptamer for Enhanced Functional Protein Delivery.

Authors
  • Jiang, Ying1, 2
  • Pan, Xiaoshu2
  • Chang, Jin3, 4
  • Niu, Weijia2
  • Hou, Weijia2
  • Kuai, Hailan1
  • Zhao, Zilong1
  • Liu, Ji3, 4
  • Wang, Ming3, 4
  • Tan, Weihong1, 5, 2
  • 1 Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Life Sciences, Aptamer Engineering Center of Hunan Province , Hunan University , Changsha , Hunan 410082 , People's Republic of China. , (China)
  • 2 Center for Research at Bio/Nano Interface, Department of Chemistry and Department of Physiology and Functional Genomics, Shands Cancer Center, UF Genetics Institute and McKnight Brain Institute , University of Florida , Gainesville , Florida 32611-7200 , United States. , (United States)
  • 3 Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry , Chinese Academy of Sciences , Beijing 100190 , People's Republic of China. , (China)
  • 4 University of Chinese Academy of Sciences , Beijing 100049 , People's Republic of China. , (China)
  • 5 Institute of Molecular Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, and College of Chemistry and Chemical Engineering , Shanghai Jiao Tong University , Shanghai 200240 , People's Republic of China. , (China)
Type
Published Article
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society
Publication Date
Jun 06, 2018
Volume
140
Issue
22
Pages
6780–6784
Identifiers
DOI: 10.1021/jacs.8b03442
PMID: 29772170
Source
Medline
License
Unknown

Abstract

Circular bivalent aptamers (cb-apt) comprise an emerging class of chemically engineered aptamers with substantially improved stability and molecular recognition ability. Its therapeutic application, however, is challenged by the lack of functional modules to control the interactions of cb-apt with therapeutics. We present the design of a β-cyclodextrin-modified cb-apt (cb-apt-βCD) and its supramolecular interaction with molecular therapeutics via host-guest chemistry for targeted intracellular delivery. The supramolecular ensemble exhibits high serum stability and enhanced intracellular delivery efficiency compared to a monomeric aptamer. The cb-apt-βCD ensemble delivers green fluorescent protein into targeted cells with efficiency as high as 80%, or cytotoxic saporin to efficiently inhibit tumor cell growth. The strategy of conjugating βCD to cb-apt, and subsequently modulating the supramolecular chemistry of cb-apt-βCD, provides a general platform to expand and diversify the function of aptamers, enabling new biological and therapeutic applications.

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