Viral nanoparticles as tools for intravital vascular imaging

John D Lewis^1, 2, Giuseppe Destito^1, 3, 4, Andries Zijlstra^1, 2, Maria J Gonzalez^1, 3, James P Quigley^1, 2, Marianne Manchester^1, 3 & Heidi Stuhlmann^1, 2

¹  Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.

²  Division of Vascular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.

³  Center for Integrative Molecular Biosciences, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.

⁴  Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi Magna Graecia di Catanzaro, Viale Europa, Campus Universitario di Germaneto, 88100, Catanzaro, Italy.

A significant impediment to the widespread use of noninvasive in vivo vascular imaging techniques is the current lack of suitable intravital imaging probes. We describe here a new strategy to use viral nanoparticles as a platform for the multivalent display of fluorescent dyes to image tissues deep inside living organisms. The bioavailable cowpea mosaic virus (CPMV) can be fluorescently labeled to high densities with no measurable quenching, resulting in exceptionally bright particles with in vivo dispersion properties that allow high-resolution intravital imaging of vascular endothelium for periods of at least 72 h. We show that CPMV nanoparticles can be used to visualize the vasculature and blood flow in living mouse and chick embryos to a depth of up to 500 m. Furthermore, we show that the intravital visualization of human fibrosarcoma-mediated tumor angiogenesis using fluorescent CPMV provides a means to identify arterial and venous vessels and to monitor the neovascularization of the tumor microenvironment.

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