title: Retargeting Polyomavirus-Like Particles to Cancer Cells by Chemical Modification of Capsid Surface.
abstract: Virus-like particles based on polyomaviruses (PVLPs) are promising delivery devices for various cargoes, including nucleic acids, imaging probes, and therapeutic agents. In biological environments, the major coat protein VP1 interacts with ubiquitously distributed sialic acid residues, and therefore PVLPs show a broad tropism. For selective targeting, appropriate engineering of the PVLP surface is needed. Here, we describe a chemical approach to retarget PVLPs to cancer cells displaying abnormally high levels of transferrin receptor. We created an array of transferrin molecules on the surface of PVLPs by combining a high-yielding bioconjugation approach with specific point modification of transferrin. This artificial surface protein architecture enables (i) suppression of natural VP1-specific interactions by blocking the surface conformational epitope on the VP1 protein, (ii) unusually high cellular uptake efficiency, and (iii) selective retargeting of PVLPs to osteosarcoma (U2OS) and lymphoblastoid leukemia (CCRF-CEM) cells.
authors.affiliation: Department of Genetics and Microbiology, Faculty of Science, Charles University , Vinicna 5, 128 44 Prague 2, Czech Republic.
authors.forename: Jirina
authors.initials: J
authors.lastname: Zackova Suchanova
authors.affiliation: Institute of Organic Chemistry and Biochemistry of the CAS , v.v.i., Flemingovo nam. 2, 166 10, Prague 6, Czech Republic.|First Faculty of Medicine, Charles University , Katerinska 32, 121 08, Prague 2, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Neburkova
authors.affiliation: Department of Genetics and Microbiology, Faculty of Science, Charles University , Vinicna 5, 128 44 Prague 2, Czech Republic.|Institute of Organic Chemistry and Biochemistry of the CAS , v.v.i., Flemingovo nam. 2, 166 10, Prague 6, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Spanielova
authors.affiliation: Department of Genetics and Microbiology, Faculty of Science, Charles University , Vinicna 5, 128 44 Prague 2, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Forstova
authors.affiliation: Institute of Organic Chemistry and Biochemistry of the CAS , v.v.i., Flemingovo nam. 2, 166 10, Prague 6, Czech Republic.
authors.forename: Petr
authors.identifier: 0000-0003-0283-647X
authors.initials: P
authors.lastname: Cigler
mesh_terms: D001692:Biological Transport; D002213:Capsid / Q000737:chemistry* / Q000378:metabolism; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D011120:Polyomavirus / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D004337:Drug Carriers