title: Dual-functionalized graphene oxide for enhanced siRNA delivery to breast cancer cells.
abstract: The aim of this study is to improve hydrocolloid stability and siRNA transfection ability of a reduced graphene oxide (rGO) based nano-carrier using a phospholipid-based amphiphilic polymer (PL-PEG) and cell penetrating peptide (CPPs). The dual functionalized nano-carrier is comprehensively characterized for its chemical structure, size, surface charge and morphology as well as thermal stability. The nano-carrier cytocompatibility, siRNA condensation ability both in the presence and absence of enzyme, endosomal buffering capacity, cellular uptake and intracellular localization are also assessed. The siRNA loaded nano-carrier is used for internalization to MCF-7 cells and its gene silencing ability is compared with AllStars Hs Cell Death siRNA as a model gene. The nano-carrier remains stable in biological solution, exhibits excellent cytocompatibility, retards the siRNA migration and protects it against enzyme degradation. The buffering capacity analysis shows that incorporation of the peptide in nano-carrier structure would increase the resistance to endo/lysosomal like acidic condition (pH 6-4) The functionalized nano-carrier which is loaded with siRNA in an optimal N:P ratio presents superior internalization efficiency (82±5.1% compared to HiPerFect(®)), endosomal escape quality and capable of inducing cell death in MCF-7 cancer cells (51±3.1% compared to non-treated cells). The success of siRNA-based therapy is largely dependent on the safe and efficient delivery system, therefore; the dual functionalized rGO introduced here could have a great potential to be used as a carrier for siRNA delivery with relevancy in therapeutics and clinical applications.
authors.affiliation: Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine, McGill University, Montréal, QC H3A 2B4, Canada; Department of Biomedical Engineering, Amirkabir University of Technology, Tehran 15875/4413, Iran.
authors.forename: Rana
authors.initials: R
authors.lastname: Imani
authors.affiliation: Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine, McGill University, Montréal, QC H3A 2B4, Canada.
authors.forename: Wei
authors.initials: W
authors.lastname: Shao
authors.affiliation: Department of Computer and Software Engineering, Institute of Biomedical Engineering, Polytechnique Montréal, Montréal, Québec H3C3A7, Canada.
authors.forename: Samira
authors.initials: S
authors.lastname: Taherkhani
authors.affiliation: Department of Biomedical Engineering, Amirkabir University of Technology, Tehran 15875/4413, Iran.
authors.forename: Shahriar Hojjati
authors.initials: SH
authors.lastname: Emami
authors.affiliation: Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Faculty of Medicine, McGill University, Montréal, QC H3A 2B4, Canada. Electronic address: satya.prakash@mcgill.ca.
authors.forename: Satya
authors.initials: S
authors.lastname: Prakash
authors.affiliation: Tissue Engineering and Biomaterials Research Center, National Institute of Genetic Engineering and Biotechnology, Tehran 14965/161, Iran. Electronic address: sfaghihi@nigeb.ac.ir.
authors.forename: Shahab
authors.initials: S
authors.lastname: Faghihi
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D049109:Cell Proliferation / Q000235:genetics*; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D020868:Gene Silencing; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010087:Oxides / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D010087:Oxides; D034741:RNA, Small Interfering; D006108:Graphite
keywords: Amphiphilic polymer; Cell penetrating peptide; Gene delivery; Graphene oxide; Nano-carrier; siRNA