title: SRL-Coated PAMAM Dendrimer Nano-Carrier for Targeted Gene Delivery to the Glioma Cells and Competitive Inhibition by Lactoferrin.
abstract: Glioma, as a primary tumor of central nervous system, is the main cause of death in patients with brain cancer. Therefore, development of an efficient strategy for treatment of glioma is worthy. The aim of the current study was to develop a SRL peptide-coated dendrimer as a novel dual gene delivery system for targeting the LRP receptor, an up-regulated gene in both BBB and glioma cells. To perform this investigation, our newly developed nanocarrier (PAMAM-PEG-SRL) was used for gene delivery to C6 glioma cell lines. DNA (GFP) was loaded in these functionalized nanoparticles and their cellular uptake/distribution and gene transfection efficacy was evaluated by fluorescence and confocal microscopy. In vitro studies showed that SRL-modified nanoparticles have good transfection efficacy. Results revealed improved gene transfection efficiency of newly-synthesized delivery system. We also found that lactoferrin, as a LRP ligand, reduced the gene transfection efficacy of the delivery system due to its higher affinity compared to SRL peptides (Competitive inhibition). The present results suggest that the synthesized delivery system has the potential to be used as an alternative targeted drug delivery system for brain tumors.
authors.affiliation: Biomedical Engineering and Medical Physics Department, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Zarebkohan
authors.affiliation: Department of Resin and Additives, Institute for Color Science and Technology, Tehran, Iran.
authors.forename: Farhood
authors.initials: F
authors.lastname: Najafi
authors.affiliation: School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Moghimi
authors.affiliation: Biomedical Engineering and Medical Physics Department, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Hemmati
authors.affiliation: Biomedical Engineering and Medical Physics Department, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Deevband
authors.affiliation: Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.; Department of Biotechnology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Bahram
authors.initials: B
authors.lastname: Kazemi
keywords: Brain tumor; C6 glioma; Gene delivery; PAMAM dendrimer; SRL peptide; Targeted delivery