Abstract
Gene therapy is used to correct or compensate for diseases caused by gene defects and abnormalities. Improving the transfection efficiency and reducing the toxicity of gene carriers are the keys to gene therapy. Similar to a typical cationic gene carrier—polyethylenimine (PEI, 25 kDa)—the polyamidoamine (PAMAM) dendrimer also has a large number of amino groups. These amino groups can be complexed with nucleic acids after protonation under physiological conditions. However, the concentrated positive charge can cause undesirable cytotoxicity. Cellulose nanocrystals (CNCs) have good biocompatibility and unique needle-like morphology, and have been proven to be efficiently taken up by cells. In this article, three-dimensional spherical PMAMA dendrimers are conjugated onto the surface of CNCs to obtain a kind of needle-like cationic carrier (CNC-PAMAM). PAMAM dendrimers act as anchors to bind the plasmid DNAs (pDNA) to the surface of the CNC. The prepared CNC-based carrier showed high transfection efficiency and low toxicity. The CNC-PAMAM can effectively deliver the suicide gene to the tumor site, enabling the suicide gene/prodrug system (cytosine deaminase/5-fluorocytosine (CD/5-FC)) to play an effective anti-tumor role in vivo. This research demonstrates that the functionalization of CNCs with PAMAM dendrimers is an effective method for developing novel gene delivery systems.
Highlights
IntroductionThe nucleic acid is degraded by ribozymes in tissues or cells
PAMAM dendrimers were synthesized by using MA and EDA as reported in our previous publication [22]
PAMAM dendrimers were successfully conjugated to the surface of Cellulose nanocrystals (CNCs), and needlePAMAM dendrimers were successfully conjugated to the surface of CNCs, and neelike nanoparticles with cationic shells were obtained
Summary
The nucleic acid is degraded by ribozymes in tissues or cells. The naked nucleic acid cannot be directly administered by oral administration or injection, but a gene carrier is required [4,5]. Gene carriers can help nucleic acids overcome various barriers in blood vessels, the extracellular matrix, and cells [6,7,8]. Non-viral vectors have the advantages of low cost, simple preparation, convenient large-scale production, high safety, and unlimited length of exogenous genes [9]. Cationic gene carriers, such as cationic polymers, cationic polypeptides, and cationic liposomes, are the most studied non-viral gene carriers [10,11,12]. The structure of the cationic gene carrier needs to be precisely designed to balance its efficiency and toxicity
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