Fluorescent Tobacco mosaic virus-Derived Bio-Nanoparticles for Intravital Two-Photon Imaging

Abstract

Multi-photon intravital imaging has become a powerful tool to investigate the healthy and diseased brain vasculature in living animals. Although agents for multi-photon fluorescence microscopy of the microvasculature are available, issues related to stability, bioavailability, toxicity, cost or chemical adaptability remain to be solved. In particular, there is a need for highly fluorescent dyes linked to particles that do not cross the blood brain barrier (BBB) in brain diseases like tumor or stroke to estimate the functional blood supply. Plant virus particles possess a number of distinct advantages over other particles, the most important being the multi-valency of chemically addressable sites on the particle surface. This multi-valency, together with biological compatibility and inert nature, makes plant viruses ideal carriers for in vivo imaging agents. Here, we show that the well-known Tobacco mosaic virus is a suitable nanocarrier for two-photon dyes and for intravital imaging of the mouse brain vasculature.

Recent Advancements of Nanomedicine towards Antiangiogenic Therapy in Cancer

“…Similarly, a fluorescent plant VNPs with specific targeting ligands TMV-BF3 were developed for intravital imaging of the mouse brain vasculature (Figure 8). Further, these VNPs were used for delivery of therapeutic agents such as drugs or peptides and may lead to the development of novel cost-effective tools for in vivo theranostics [140]. Regardless of the enormous development in VEGF mediated antiangiogenic therapies available for therapeutic use, clinical evidence is escalating to recommend that targeting only VEGF may not be effective in inhibiting tumor angiogenesis.…”

“…The 3D projections were performed with Fiji software using the standard deviation projection method. Reproduced with permission from[140]. Copyright, 2016, Frontiers.…”

Understanding the In Vivo Fate of Advanced Materials by Imaging

“…[253] Fluorescently labeled Tobacco mosaic virus was recently used to monitor the blood flow inside the brain using two-photon microscopy. [254] More recently, a label-free functional photoacoustic IVM method was described to record the fast-changing fluid dynamic and oxygenation conditions in brain vasculatures. [79] Combined, these novel IVM techniques can thus aid in the evaluation of PK and biodistribution of materials targeting brain.…”

Synthetic plant virology for nanobiotechnology and nanomedicine

“…116,117 Recently the coupling of TMV particles to the two-photon dye BF 3 -NCS has been demonstrated to allow visualization of diseased brain vasculature in mice. 118 Imaging using nonoptical methods such as MRI is also achievable by loading metals such as gadolinium into VNPs. 119,120 Such metal-VNPspecific interactions, referred to as mineralization, are further discussed in Section Mineralization of Viral Scaffolds.…”