Cancer 2013 July-12

 

Enhanced Cellular Uptake and Gene Delivery of Glioblastoma with Deferoxamine-coated Nanoparticle/Plasmid DNA/Branched Polyethylenimine Composites.

Chem Commun (Camb). 2013 Jan 21;49(6):549-51.

Leung KCF, Chak CP, Lee SF, Lai JMY, Zhu XM, Wang YXJ, Sham KWY, Cheng CHK

Department of Chemistry and Institute of Creativity, The Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong SAR, P. R. China

Abstract

Ternary composite nanomaterials based on deferoxamine-coated superparamagnetic iron oxide nanoparticle (8-10 nm), circular plasmid DNA (~4 kb) with fluorescent/luminescent reporter group, and branched polyethylenimine (25 kDa, PDI=2.5) were prepared and compared their efficiencies in transfecting brain tumor cells at low concentration.

PMID: 23192002

 

Additional summary:

Although brain tumor (glioblastoma) cells have had their genomic sequence revealed recently, there is only limited success in treating human glioblastoma because of its aggressive malignant nature. To this end, nanotechnology has played a role to advance the biomedical research field by developing new nanomaterials for simultaneous diagnosis and therapy, i.e., theranostic purposes. In light of the interim success in labelling brain tumor cells with different forms or surface functionalities of nanoparticles towards gliobalstoma treatment, in principle, a novel composite nanomaterial, is yet to be developed for potential gene transfer, drug delivery, and magnetic resonance imaging (MRI) enhancement, simultaneously. In this paper, we report novel ternary composite nanomaterials that contain deferoxamine-coated superparamagnetic iron oxide nanoparticles (NP), circular plasmid DNAs (pDNAs: pEGFP-C1 and pRL-CMV), and branched polyethylenimine (PEI, 25 kDa, PDI = 2.5), potentially suitable for proposed applications. Branched PEI possesses lower chain flexibility than linear PEI, so as to enhance the stability and maintain the morphology of the resulting complexes. Moreover, a lower amount of branched PEI can be employed for forming the stable ternary complex, thus reducing the cytotoxicity. Deferoxamine is used clinically to treat iron poisoning, as it binds ferric ions in the blood stream and enhances its elimination in urine. pEGFP-C1 is a pDNA of ~4.7 kb encoded with a red-shifted variant of wild-type green fluorescence protein (GFP) in mammalian cells. pRL-CMV is a pNDA of ~4.0 kb encoded with Renilla luciferase (RLU) in various cell types. These two pDNAs are commonly used for studying transfection efficiencies as markers. The fluorescence/luminescence intensity is directly proportional to the amount of GFP/RLU which can be easily detected by their strong, enhanced and constitutive expression of the reporters, and can be optimized to express in a variety of cell types/lines. Superparamagnetic iron oxide nanoparticles (SPIO-NPs) such as ferumoxides and ferucarbotran have been used clinically as contrast agents for MRI in liver. Ultrasmall SPIO-NPs are employed and attached, at their peripheries, with deferoxamine ligand which is used as an adhesive material between pDNAs and branched PEI via multiple hydrogen bonds and electrostatic interaction. For related research work, see: Int. J. Nanomed. 2012;7:953-64; Chem.-Asian J. 2013;8:1760-64; Methods. 2013;DOI:10.1016/j.ymeth.2013.06.006.

 

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