The Application of Plant Viral Nanoparticles in Tissue-Specific Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 393

of “smart” targeted nanoparticles, which combine targeting molecules with therapeutic
and/or imaging agents all within one entity. These targeted nanoparticles hold promise
for delivery of imaging agents and drugs to disease sites, resulting in the production
of high contrast images with reduced noise levels as well as increased efficacy of
therapy with reduced adverse side effects. Nanoparticles hold several key advanta-
geous features: (i) multivalency, which allows for the integration of multiple target-
ing, imaging, and therapeutic agents within one platform; (ii) large surface area for
functionalization with targeting ligands and extensive cargo volume for loading with
imaging agents and therapeutic drugs; and (iii) suitable size and surface properties
that enable them to have a prolonged blood circulation time and reduced uptake into
the reticuloendothelial system (reS) (reviewed in refs. [1-3]).
Several nanoparticles have been developed from various naturally occurring organic
(lipids [4], proteins [5], polymers [6], etc.) and inorganic (gold [7, 8], silica [9], iron
[10, 11], see chapter 3) building blocks. The inherent nature of the building blocks
utilized can significantly (see also chapter 2) impact the physiochemical properties
and function of the nanoparticles, offering investigators numerous choices to serve
their specific purpose [12]. More than 25 nanoscale platforms have been approved for
clinical use, including peGylated liposomes containing doxorubicin (Doxil/Caelyx),
albumin-bound nanoparticles of paclitaxel (Abraxane), and poly(lactic-co-glycolic
acid) (pLGA) nanoparticles for drug delivery; superparamagnetic iron oxide
nanoparticle contrast agents for magnetic resonance imaging (Mri) (GastroMArK);
and virus-based vaccines (Gardasil) (reviewed in refs. [13-15]). Although inorganic
nanoparticles offer several advantages, such as wide availability, controlled shape and
size, and easy surface manipulation, they generally have poor stability under aqueous
conditions and low cellular transfer efficiency [12, 16]. Lipid-based nanoparticles such
as liposomes and micelles can carry significant drug payloads, yet they suffer from
poor in vivo stability [16, 17]. Nanomaterials comprised of plant viruses have qualities
that address many of these limitations. Viral nanoparticles (VNps) come in many
shapes and sizes. Because the function of the viral capsid is to protect its genome under
varying environmental conditions, they are naturally stable and monodisperse. VNps
combine the strengths of inorganic and lipid-based materials; essentially, they can be
regarded as a fancy polymer assembled with atomic precision.
VNps derived from plants or bacteria provide an ideal basis for the generation of
targeted imaging agents and drug delivery vehicles (reviewed in refs. [15, 18]). Viruslike
particles (VLps) are a subset of VNps that can be produced in a heterologous expression
systems at a large scale but lack any replicative genomic information. Thus, VLps of
eukaryotic viruses are safe, noninfectious, and nonhazardous for use in humans and
other mammals (reviewed in ref. [19]). VNps and VLps are self-assembling systems
that are highly symmetrical, dynamic, polyvalent, and monodisperse, rendering them
one of the most advanced nanomaterials produced in nature. They offer the advantages
of biocompatibility and biodegradability over synthetic inorganic nanoparticles. in
addition, they are extremely robust and well characterized and can be produced in large
quantities within a short period of time [18]. The structure of VNps can be modified in
several ways to allow for the loading of drugs, imaging agents, and other nanoparticles
within the internal cavity, as well as chemical conjugation of targeting ligands on the
external surface for tissue-specific delivery [20].