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Polyethylene glycol and octaarginine n dual‐functionalized nano‐graphene oxide: An optimization for efficient nucleic acids delivery

Abstract

The successful application of nucleic acid-based therapy for the treatment of various cancers is largely dependent on a safe and efficient delivery system. A dual-functionalized graphene oxide (GO)-based nanocarrier with conjugation of aminated-polyethylenglycole (PEG-diamine) and octaarginine (R8) for intracellular delivery of nucleic acids is proposed. The functionalized sites are covalently co-conjugated and the PEG:R8 molar ratio optimized at 10:1 to achieve a hydrocolloidally stable size of 252±2.0 nm with an effective charge of +40.97±1.05 and amine-rich content of 10.87±0.4 umol/g. The uptake of the nanocarrier in breast cancer cell lines, MCF-7 and MDA-MB 231, is investigated. siRNA and pDNA condensation ability in the presence and absence of enzymes and endosomal buffering capacity, as well as the intracellular localization of gene/nanocarriercomplex is also evaluated. Furthermore, the delivery of functional genes associated with the nanocarrier is assessed using c-Myc protein knock down and EGFP gene expression. The effective uptake of the nanocarrier by the cells shows superior cytocompatibility, protects the siRNA and pDNA against enzyme degradation while inhibiting their migration with N:P ratios of 10 and 5, respectively. The co-conjugation of PEG-diamine and cationic cell penetrating peptide (CPP) into the GO nanocarrier also provides a superior internalization efficacy of 85% in comparison to a commercially available transfection reagent. The c-Myc protein knock down and EGFP expression, which are induced by the nanocarrier, confirm the optimized PEG-diamine/R8 functionalized GO could effectively deliver pDNA and siRNA into the cells and interfere with gene expression.

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Publication details

The article was received on 15 Jan 2018, accepted on 16 Apr 2018 and first published on 17 Apr 2018


Article type: Paper
DOI: 10.1039/C8BM00058A
Citation: Biomater. Sci., 2018, Accepted Manuscript
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    Polyethylene glycol and octaarginine n dual‐functionalized nano‐graphene oxide: An optimization for efficient nucleic acids delivery

    R. Imani, S. Prakash, H. Vali and S. Faghihi, Biomater. Sci., 2018, Accepted Manuscript , DOI: 10.1039/C8BM00058A

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