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.

Titanium Dioxide Nanoparticle-Induced Oxidative Stress Triggers DNA Damage and Hepatic Injury in Mice

“…This may imply that decoration of PVX with 380 PEG5000 chains is insufficient to achieve effective shielding from uptake in antigen-presenting cells. This is an important observation because the development of VNPs thus far has focused on the use of low-molecular-weight PEG chains, such as PEG500 [41], PEG1000 and PEG2000 [42]. Further research is therefore required to determine exactly how VNPs based on plant viruses interact with the immune system and whether shielding chemistries, such as PEGylation, are sufficient to prevent immunogenicity (see ‘Conclusion’ section).…”

“…Variables to test are the PEGylation density, confirmation and attachment sites. Research on VNPs has focused on the application of low-molecular-weight PEG chains such as PEG500 [41], PEG1000 and PEG2000 [42]. We report here the application of PEG5000.…”

Gastrin-releasing peptide receptor-targeted gadolinium oxide-based multifunctional nanoparticles for dual magnetic resonance/fluorescent molecular imaging of prostate cancer

“…BBN, CGGG-QWAVGHLM-NH2 (7)(8)(9)(10)(11)(12)(13)(14), was synthesized using standard fluorenylmethoxycarbonyl (fmoc) chemistry solid phase peptide synthesis method by Boxin Biotechnology (Xiamen, People's Republic of China). All other chemicals were used without further purification.…”

“…The long hydrophilic polyethylene glycol (PEG) segments bearing BBN ligand facilitated specific binding to the overexpressed GRPR, which increased tumor selectivity. 13 Then, the physicochemical properties and cytotoxicity of Gd 2 O 3 -based nanoprobes were investigated. Cellular uptake efficiency was evaluated by fluorescence microscopy, flow cytometry and in vitro MRI.…”

A supramolecular strategy to assemble multifunctional viral nanoparticles

“…3,4 Recently, inspired by the hierarchical structures of biogenic viral particles, multifunctional virus-like nanostructures have been constructed from synthetic polymers. 5,6 In the meantime, the application of viral nanoparticles (VNPs) derived from plants and bacteria in biomedical fields has also attracted great attention, primarily due to their well-defined, programmable, multivalent and monodispersed structural features [7][8][9][10][11][12][13][14][15][16][17][18][19] as well as their good biocompatibility. 20,21 To make the best use of the inherent compositions and structures of VNPs, many multifunctional VNPs have been constructed by the combination of mutagenesis and bioconjugation approaches, by which a variety of targeting ligands, catalytic units, diagnostic probes and therapeutic cargos have been anchored on the surface or inside of the internal cavity of VNPs.…”