title: Graphene nanoribbons elicit cell specific uptake and delivery via activation of epidermal growth factor receptor enhanced by human papillomavirus E5 protein.
abstract: Ligands such as peptides, antibodies or other epitopes bind and activate specific cell receptors, and are employed for targeted cellular delivery of pharmaceuticals such as drugs, genes and imaging agents. Herein, we show that oxidized graphene nanoribbons, non-covalently functionalized with PEG-DSPE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N[amino(polyethyleneglycol)]) (O-GNR-PEG-DSPE) activate epidermal growth factor receptors (EGFRs). This activation generates a predominantly dynamin-dependent macropinocytosis-like response, and results in significant O-GNR-PEG-DSPE uptake into cells with high EGFR expression. Cells with an integrated human papillomavirus (HPV) genome also show increased uptake due to the modulation of the activated EGFR by the viral protein E5. We demonstrate that this cell specific uptake of O-GNR-PEG-DSPE can be exploited to achieve significantly enhanced drug efficacies even in drug resistant cells. These results have implications for the development of active targeting and delivery agents without ligand functionalization for use in the diagnosis and treatment of pathologies that overexpress EGFR or mediated by HPV.
authors: Department of Biomedical Engineering, Bioengineering Building, Room 115, Stony Brook University, Stony Brook, NY 11794-5281, USA.
authors: Sayan
authors: S
authors: Mullick Chowdhury
authors: Department of Biomedical Engineering, Bioengineering Building, Room 115, Stony Brook University, Stony Brook, NY 11794-5281, USA.
authors: Prady
authors: P
authors: Manepalli
authors: Department of Biomedical Engineering, Bioengineering Building, Room 115, Stony Brook University, Stony Brook, NY 11794-5281, USA. Electronic address: balaji.sitharaman@stonybrook.edu.
authors: Balaji
authors: B
authors: Sitharaman
mesh_terms: D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D016679:Genome, Viral; D006108:Graphite / Q000737:chemistry*; D006367:HeLa Cells; D052162:Human papillomavirus 16; D006801:Humans; D037742:Nanotubes, Carbon / Q000737:chemistry*; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D010873:Pinocytosis; D000086082:Viroporin Proteins
chemical_list: D066246:ErbB Receptors; D006108:Graphite; D037742:Nanotubes, Carbon; D009856:Oncogene Proteins, Viral; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins; C512478:EGFR protein, human
keywords: Drug delivery; Epidermal growth factor receptors; Graphene nanoribbons; Human papillomavirus protein E5; Uptake mechanism