title: Intravital imaging of human prostate cancer using viral nanoparticles targeted to gastrin-releasing Peptide receptors.
abstract: Multivalent nanoparticles have several key advantages in terms of solubility, binding avidity, and uptake, making them particularly well suited to molecular imaging applications. Herein is reported the stepwise synthesis and characterization of NIR viral nanoparticles targeted to gastrin-releasing peptide receptors that are over-expressed in human prostate cancers. The pan-bombesin analogue, [β-Ala11, Phe13, Nle14]bombesin-(7-14), is conjugated to cowpea mosaic virus particles functionalized with an NIR dye (Alexa Fluor 647) and polyethylene glycol (PEG) using the copper(I)-catalyzed azide-alkyne cycloaddition reaction. Targeting and uptake in human PC-3 prostate cells is demonstrated in vitro. Tumor homing is observed using human prostate tumor xenografts on the chicken chorioallantoic membrane model using intravital imaging. Further development of this viral nanoparticle platform may open the door to potential clinical noninvasive molecular imaging strategies.
authors.affiliation: Department of Cell Biology, Center of Integrative Molecular Biosciences, The Scripps Research Institute, North Torrey Pines Rd., La Jolla, CA 92037, USA.
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Steinmetz
authors.forename: Amber L
authors.initials: AL
authors.lastname: Ablack
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Hickey
authors.forename: Jailal
authors.initials: J
authors.lastname: Ablack
authors.forename: Bhavik
authors.initials: B
authors.lastname: Manocha
authors.forename: Joe S
authors.initials: JS
authors.lastname: Mymryk
authors.forename: Leonard G
authors.initials: LG
authors.lastname: Luyt
authors.forename: John D
authors.initials: JD
authors.lastname: Lewis
mesh_terms: D000818:Animals; D001839:Bombesin / Q000737:chemistry; D045744:Cell Line, Tumor; D002645:Chickens; D017798:Comovirus / Q000737:chemistry; D006801:Humans; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000473:pathology*; D018004:Receptors, Bombesin / Q000378:metabolism*
chemical_list: D018004:Receptors, Bombesin; D011092:Polyethylene Glycols; D001839:Bombesin