Abstract
The carbon-based nanomaterial graphene can be chemically modified to associate with various molecules such as chemicals and biomolecules and developed as novel carriers for drug and gene delivery. In this study, a nonviral gene transfection reagent was produced by functionalizing graphene oxide (GO) with a polycationic polymer, polyethylenimine (PEI), to increase the biocompatibility of GO and to transfect small interfering RNA (siRNA) against C-X-C chemokine receptor type 4 (CXCR4), a biomarker associated with cancer metastasis, into invasive breast cancer cells. PEI-functionalized GO (PEI-GO) was a homogeneous aqueous solution that remained in suspension during storage at 4 °C for at least 6 months. The particle size of PEI-GO was 172 ± 4.58 and 188 ± 5.00 nm at 4 and 25 °C, respectively, and increased slightly to 262 ± 17.6 nm at 37 °C, but remained unaltered with time. Binding affinity of PEI-GO toward siRNA was assessed by electrophoretic mobility shift assay (EMSA), in which PEI-GO and siRNA were completely associated at a PEI-GO:siRNA weight ratio of 2:1 and above. The invasive breast cancer cell line, MDA-MB-231, was transfected with PEI-GO in complex with siRNAs against CXCR4 (siCXCR4). Suppression of the mRNA and protein expression of CXCR4 by the PEI-GO/siCXCR4 complex was confirmed by real-time PCR and western blot analysis. In addition, the metastatic potential of MDA-MB-231 cells was attenuated by the PEI-GO/siCXCR4 complex as demonstrated in wound healing assay. Our results suggest that PEI-GO is effective in the delivery of siRNA and may contribute to targeted gene therapy to suppress cancer metastasis.
Highlights
Graphene oxide (GO) is a carbon-based nanomaterial with a single layer of carbon molecules covalently linked to oxidized functional groups such as carboxyl (–COOH) and hydroxyl (–OH) groups, which can be chemically modified to increase its biocompatibility in order to associate with drugs and biomolecules [1]
We explored the potential of PEI-functionalized GO (PEI-GO) in the transfection of small interfering RNA (siRNA) against CXCR4 to suppress the migration of MDA-MB-231 cells, a metastatic cancer cell line overexpressing CXCR4
Our results suggest that PEI-GO is a potentially efficient nonviral transfection reagent that may contribute to targeted cancer therapy
Summary
Graphene oxide (GO) is a carbon-based nanomaterial with a single layer of carbon molecules covalently linked to oxidized functional groups such as carboxyl (–COOH) and hydroxyl (–OH) groups, which can be chemically modified to increase its biocompatibility in order to associate with drugs and biomolecules [1]. PEI-functionalized GO (PEI-GO) successfully delivered both small interfering RNA (siRNA) and anticancer drugs to enhance chemotherapeutic effect in cancer cells [9]. (NIR) optical absorbance of GO, photothermally controlled delivery of siRNA and plasmid DNA by GO functionalized with both PEI and polyethylene glycol (PEG) was achieved [23, 24]. Drug and gene delivery systems based on nanomaterials are designed to target against CXCR4 and facilitate cancer therapy and imaging. PEG-functionalized carbon nanotube and cationic dextran-based nanoparticles were reported to deliver siRNA against CXCR4 into primary cells and animal model for colorectal cancer [32, 33]. Peptide ligands and peptide dendrimers against CXCR4 were used alone or in conjugation with nanoparticles to deliver anticancer drugs, inhibit tumor metastasis, and enhance molecular imaging [34,35,36,37]. Synthetic polycationic viologen dendrimers (VGD) targeting CXCR4 were developed to facilitate targeted delivery of plasmid DNAs and cancer therapy [38]
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