title: Suppression of Breast Cancer Cell Migration by Small Interfering RNA Delivered by Polyethylenimine-Functionalized Graphene Oxide.
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.
authors.affiliation: Department of Cosmetics and Fashion Styling, Cheng Shiu University, Kaohsiung, Taiwan.
authors.forename: Yuan-Pin
authors.initials: YP
authors.lastname: Huang
authors.affiliation: Department of General Surgery, E-Da Hospital, Kaohsiung, Taiwan.
authors.forename: Chao-Ming
authors.initials: CM
authors.lastname: Hung
authors.affiliation: Graduate Institute of Medical Sciences, Chang Jung Christian University, Tainan, Taiwan.|Innovative Research Center of Medicine, Chang Jung Christian University, Tainan, Taiwan.
authors.forename: Yi-Chiang
authors.initials: YC
authors.lastname: Hsu
authors.affiliation: Department of Bioscience Technology, Chang Jung Christian University, No. 1 Changda Rd., Gueiren District, Tainan City, 71101, Taiwan.
authors.forename: Cai-Yan
authors.initials: CY
authors.lastname: Zhong
authors.affiliation: Department of Bioscience Technology, Chang Jung Christian University, No. 1 Changda Rd., Gueiren District, Tainan City, 71101, Taiwan.
authors.forename: Wan-Rou
authors.initials: WR
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, E-Da Hospital, Kaohsiung, Taiwan.
authors.forename: Chi-Chang
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Innovative Research Center of Medicine, Chang Jung Christian University, Tainan, Taiwan. mjlee@mail.cjcu.edu.tw.|Department of Bioscience Technology, Chang Jung Christian University, No. 1 Changda Rd., Gueiren District, Tainan City, 71101, Taiwan. mjlee@mail.cjcu.edu.tw.
authors.forename: Mon-Juan
authors.initials: MJ
authors.lastname: Lee
keywords: C-X-C chemokine receptor type 4 (CXCR4); Cancer cell migration; Graphene oxide (GO); Polyethylenimine (PEI); Small interfering RNA (siRNA)