Guiding plant virus particles to integrin-displaying cells

Marisa L. Hovlid; Nicole F. Steinmetz; Burkhardt Laufer; Jolene L. Lau; Jane Kuzelka; Qian Wang; Timo Hyypiä; Glen R. Nemerow; Horst Kessler; Marianne Manchester; M. G. Finn

doi:10.1039/C2NR30571B

Guiding plant virus particles to integrin-displaying cells†

Marisa L. Hovlid,^a Nicole F. Steinmetz,^b Burkhardt Laufer,^a Jolene L. Lau,^a Jane Kuzelka,^a Qian Wang,^a Timo Hyypiä,^c Glen R. Nemerow,^c Horst Kessler,^de Marianne Manchester*^f and M. G. Finn*^a

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^a Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA
E-mail: mgfinn@scripps.edu

^b Departments of Biomedical Engineering, Radiology, Materials Science and Engineering, Case Western Reserve University, Cleveland, OH 44106, USA

^c Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA

^d Institute for Advanced Study and Center for Integrated Protein Science, Department Chemie, Technische Universität München, D-85747 Garching, Germany

^e Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia

^f Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA 92093, USA

Abstract

Viral nanoparticles (VNPs) are structurally regular, highly stable, tunable nanomaterials that can be conveniently produced in high yields. Unmodified VNPs from plants and bacteria generally do not show tissue specificity or high selectivity in binding to or entry into mammalian cells. They are, however, malleable by both genetic and chemical means, making them useful scaffolds for the display of large numbers of cell- and tissue-targeting ligands, imaging moieties, and/or therapeutic agents in a well-defined manner. Capitalizing on this attribute, we modified the genetic sequence of the Cowpea mosaic virus (CPMV) coat protein to display an RGD oligopeptide sequence derived from human adenovirus type 2 (HAdV-2). Concurrently, wild-type CPMV was modified via NHS acylation and Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) chemistry to attach an integrin-binding cyclic RGD peptide. Both types of particles showed strong and selective affinity for several different cancer cell lines that express RGD-binding integrin receptors.

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Guiding plant virus particles to integrin-displaying cells†

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Guiding plant virus particles to integrin-displaying cells

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