title: Detection and imaging of aggressive cancer cells using an epidermal growth factor receptor (EGFR)-targeted filamentous plant virus-based nanoparticle.
abstract: Molecular imaging approaches and targeted drug delivery hold promise for earlier detection of diseases and treatment with higher efficacy while reducing side effects, therefore increasing survival rates and quality of life. Virus-based nanoparticles are a promising platform because their scaffold can be manipulated both genetically and chemically to simultaneously display targeting ligands while carrying payloads for diagnosis or therapeutic intervention. Here, we displayed a 12-amino-acid peptide ligand, GE11 (YHWYGYTPQNVI), on nanoscale filaments formed by the plant virus potato virus X (PVX). Bioconjugation was used to produce fluorescently labeled PVX-GE11 filaments targeted toward the epidermal growth factor receptor (EGFR). Cell detection and imaging was demonstrated using human skin epidermoid carcinoma, colorectal adenocarcinoma, and triple negative breast cancer cell lines (A-431, HT-29, MDA-MB-231), all of which upregulate EGFR to various degrees. Nonspecific uptake in ductal breast carcinoma (BT-474) cells was not observed. Furthermore, co-culture experiments with EGFR(+) cancer cells and macrophages indicate successful targeting and partitioning toward the cancer cells. This study lays a foundation for the development of EGFR-targeted filaments delivering contrast agents for imaging and diagnosis, and/or toxic payloads for targeted drug delivery.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, Ohio 44106, United States.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Chariou
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, Ohio 44106, United States.
authors.forename: Karin L
authors.initials: KL
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, Ohio 44106, United States.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Wen
authors.affiliation: Department of Pharmacology, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, Ohio 44106, United States.
authors.forename: Neetu M
authors.initials: NM
authors.lastname: Gulati
authors.affiliation: Department of Pharmacology, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, Ohio 44106, United States.
authors.forename: Phoebe L
authors.initials: PL
authors.lastname: Stewart
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, Ohio 44106, United States.|Department of Radiology, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, Ohio 44106, United States.|Department of Materials Science and Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, Ohio 44106, United States.|Department of Macromolecular Science and Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, Ohio 44106, United States.
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Steinmetz
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism; D009369:Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010942:Plant Viruses / Q000737:chemistry* / Q000378:metabolism
chemical_list: D010455:Peptides; D066246:ErbB Receptors