VNPs as Tools for Nanomedicine - Viral Nanoparticles: Tools for Materials Science and Biomedicine - page 206

applications. In particular, non-human pathogens such as VNPs from plant
viruses or bacteriophages are less likely to interact with human receptors or
trigger signal transduction events that may lead to downstream side effects.
In general, replication or gene expression of plant VNPs or bacteriophages
is not supported in mammalian systems.
The use of VNPs as platforms for the design of novel formulations for use
in medicine has attracted many researchers, and the field is rapidly evolving.
This chapter summarizes recent advances in the use and development
of VNPs for potential biomedical applications. The first approaches
toward utilization of VNPs and virus-like particles (VLPs) in medicine
focused on vaccines (see Section 8.2). More recent developments utilized
labeled VNPs as imaging sensors (see Section 8.3). With regard to targeted
therapies, a range of targeted drug-carrying VNPs have been developed
and tested (see Sections 8.4 and 8.5). Last but not least, VNPs and VLPs
are exploited as vehicles for therapeutic gene delivery (see Section 8.6).
Although virus-mediated gene delivery is a very large field and beyond the
scope of this chapter, we will focus on some recent discoveries in this area.

.1 toXICIty, BIodIStrIButIon, PhArMACoKInetICS, And
IMMunogenICIty oF VnPs

When developing novel materials for potential applications in medicine it
is essential to understand the

properties of the material, including
pharmacokinetics, clearance and elimination, tissue biodistribution,
immunogenicity, and toxicity. Factors such as immunogenicity and potential
toxic effects must be elucidated in detail. Plant VNPs, VLPs, and phages can
be considered as safe from a human health perspective. Nevertheless, as of
today, there are only a few studies describing the characterization of VNP
platforms

in vivo

in vivo , as summarized below.

8.1.1 Dosage and Potenial Toxicity

The platforms Adenovirus (Ad), adeno-associated virus (AAV), and Lentivirus

have long been investigated as vectors for therapeutic gene delivery. One
major problem with these human pathogens is that, even when using
replication-deficient versions, toxic effects are induced. These platforms
cause acute induction of pro-inflammatory responses, and a dosage of 2 ×
10 Ads/kg body weight has been found to induce substantial liver injury

(Ben-Gary

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et al ., 2002; Christ et al ., 2000; Cotter & Muruve, 2005; Engler et

al ., 2004; Higginbotham et al ., 2002; Reid et al ., 2002).