期刊
NANOSCALE RESEARCH LETTERS
卷 11, 期 -, 页码 -出版社
SPRINGER
DOI: 10.1186/s11671-016-1463-0
关键词
Graphene oxide (GO); Polyethylenimine (PEI); Small interfering RNA (siRNA); C-X-C chemokine receptor type 4 (CXCR4); Cancer cell migration
资金
- Ministry of Science and Technology, Taiwan [MOST 101-2314-B-309-001-MY3, MOST 103-2633-B-309-001]
- E-Da Hospital, Kaohsiung, Taiwan [EDAHP103003, EDAHP 104002]
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 degrees 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 degrees C, respectively, and increased slightly to 262 +/- 17.6 nm at 37 degrees 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.
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