Chondroitin Sulfate-Coated DNA-Nanoplexes Enhance Transfection Efficiency by Controlling Plasmid Release from Endosomes: A New Insight into Modulating Nonviral Gene Transfection

Hongji Yan, Oommen P. Oommen, Di Yu, Joens Hilborn, Hong Qian, Oommen P. Varghese

    Research output: Contribution to journalArticleScientificpeer-review

    30 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)3907-3915
    Number of pages9
    JournalAdvanced Functional Materials
    Volume25
    Issue number25
    DOIs
    Publication statusPublished - 1 Jul 2015
    Publication typeA1 Journal article-refereed

    Keywords

    • chondroitin sulfate
    • endosomal escape
    • gene delivery
    • mesenchymal stem cells
    • nanoparticles
    • HYALURONIC-ACID
    • GROWTH-FACTOR
    • CLINICAL-TRIALS
    • IN-VITRO
    • DELIVERY
    • CELLS
    • THERAPY
    • POLYPLEXES
    • RECEPTOR
    • POLYETHYLENIMINE

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