The Application of Plant Viral Nanoparticles in Tissue-Specific Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 400

capillaries and arterioles [53]. Thus, CpMV is truly a valuable tool for intravital
imaging of tumor neovasculature.
Utilizing its endogenous interactions and biocompatibility, CpMV holds promise
as a tool for imaging vascular disease as well as tumors that express high levels
of vimentin. Some recent data suggest that CpMV could also be naturally targeted
to regions of inflammation in the central nervous system (CNS) [77]. This platform
could be optimized through the use of Nir dyes and multiphoton fluorescence
imaging to enhance the depth and sensitivity of visualization or paired with other
imaging agents, such as radiotracers.

14.4 pAssiVe TArgeTing of Tumors using fluorescenT Vnps

Systemic nanoparticle drug delivery to solid tumors is largely governed by the
enhanced permeability and retention (epr) effect, where leaky vasculature and inef-
ficient lymphatic drainage resulting from tumor hypervascularization lead to the
passive diffusion of nanocarriers to the site of disease [78]. epr-mediated tumor
homing has been demonstrated using VNps such as CpMV and pVX [40, 69, 79].
These VNp formulations were peGylated to prevent nonspecific cell interactions
and prolong plasma circulation time. in one study, CpMV nanoparticles were labeled
either internally or externally with Nir fluorophores and compared side by side in a
mouse model of colon cancer with hT-29 tumor xenografts. Twenty-four hours after
intravenous injection, the tumors were excised and imaged ex vivo . Tumor homing
was observed for both formulations, with higher fluorescence intensity observed
for internally labeled CpMV particles [79]. The results show that CpMV is suitable
for fluorescent imaging and can be further developed as a multifunctional formulation,
as interior dye loading leaves the exterior surface free for additional modification with
targeting ligands and other imaging agents.
Although most nanoparticulate systems currently under development are spherical
in shape, there is growing interest in rod-shaped particles as recent data indicate
that they have advantageous pharmacokinetic and tumor homing properties [80, 81].
it was recently shown that a similar trend also holds for VNps. Tumor homing prop-
erties of flexible pVX filaments and icosahedral CpMV particles were compared in
both the CAM and mouse tumor xenograft models. particles tagged with red or Nir
dyes were injected intravenously and observed using a fluorescence intravital
imaging platform. There was no significant difference in tumor accumulation in the
CAM model, but enhanced accumulation of pVX was found using a nude mouse
hT-29 tumor xenograft model (Fig. 14.4). Although the CAM model may not accu-
rately reflect the epr effect as a result of differences in systemic clearance in the
embryonic model, it can nevertheless provide insight on how differences in shape
affect tumor penetration behavior. The filamentous pVX particles were able to pene-
trate into the tumor core, while there was no noticeable increase of CpMV in the
tumor center (Fig. 14.4a). Furthermore, confocal images of tumor sections from both
models showed pVX spread throughout the tumor and was detected in areas where
CpMV was not apparent [40]. The superior tumor homing and tissue penetration
properties of pVX and perhaps other rod-shaped VNps can be used to advance can-
cer nanotechnology.