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Highly Efficient Multifunctional Supramolecular Gene Carrier System Self‐Assembled from Redox‐Sensitive and Zwitterionic Polymer Blocks
Author(s) -
Wen Yuting,
Zhang Zhongxing,
Li Jun
Publication year - 2014
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201303687
Subject(s) - gene delivery , phosphorylcholine , supramolecular chemistry , materials science , supramolecular polymers , transfection , polymer , nanotechnology , biophysics , gene , combinatorial chemistry , chemistry , biochemistry , biology , organic chemistry , molecule , composite material
It has been a challenge to incorporate multiple features into a single gene carrier system to overcome numerous hurdles during the gene delivery. Herein, a supramolecular approach for building a multifunctional gene carrier system is demonstrated with the functions of disulfide bond based reduction‐responsive degradation and zwitterionic phosphorylcholine based extracellular stabilization and favorable cellular uptake. The gene carrier system is self‐assembled from two molecular building blocks: one host polymer, which is a redox‐sensitive β‐cyclodextrin based cationic star polymer, and one guest polymer, which is adamantyl end capped zwitterionic phosphorylcholine based polymer. The host and guest polymers self‐assemble to integrate multiple functions into one system, based on the host‐guest interaction between β‐cyclodextrin and adamantyl moieties. With the rational designs of both building blocks, the supramolecular gene carrier system possesses excellent protein stability, serum tolerance, cellular uptake and intracellular DNA release properties, and also low cytotoxicity. These features work simultaneously to achieve exceptionally high gene transfection efficiency, which is proven in MCF‐7 cell cultures using luciferase and green fluorescence protein reporter genes. Finally, the supramolecular gene carrier is applied to deliver the therapeutic p53 anti‐cancer gene in MCF‐7 cells, showing great potential for cancer gene therapy application.