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Chondroitin Sulfate‐Coated DNA‐Nanoplexes Enhance Transfection Efficiency by Controlling Plasmid Release from Endosomes: A New Insight into Modulating Nonviral Gene Transfection
Author(s) -
Yan Hongji,
Oommen Oommen P.,
Yu Di,
Hilborn Jöns,
Qian Hong,
Varghese Oommen P.
Publication year - 2015
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.201500695
Subject(s) - transfection , endosome , gene delivery , hek 293 cells , chondroitin sulfate , electroporation , microbiology and biotechnology , reporter gene , chinese hamster ovary cell , cell culture , biology , chemistry , biochemistry , intracellular , gene expression , gene , glycosaminoglycan , genetics
Degradation of plasmid DNA (pDNA) in the endosome compartment and its release to the cytosol are the major hurdles for efficient gene transfection. This is generally addressed by using transfection reagents that can overcome these limitations. In this article, the first report is presented which suggests that controlling the release of pDNA from endosome is the key for achieving efficient transfection. In this study, chondroitin sulfate (CS)‐coated DNA‐nanoplexes are developed using a modular approach where CS is coated post‐pDNA/PEI nanoplex formation. To ensure good stability of the nanoplexes, imine/enamine chemistry is exploited by reacting aldehyde‐modified chondroitin sulfate (CS‐CHO) with free amines of pDNA/PEI complex. This supramolecular nanocarrier system displays efficient cellular uptake, and controlled endosomal pDNA release without eliciting any cytotoxicity. On the contrary, burst release of pDNA from endosome (using chloroqine) results in significant reduction in gene expression. Unlike pDNA/PEI‐based transfection, the nanoparticle design presented here shows exceptional stability and gene transfection efficiency in different cell lines such as human colorectal cancer cells (HCT116), human embryonic kidney cells (HEK293), and mouse skin‐derived mesenchymal stem cells (MSCs) using luciferase protein as a reporter gene. This new insight will be valuable in designing next generation of transfection reagents.