VNPs as Tools for Nanomedicine - Viral Nanoparticles: Tools for Materials Science and Biomedicine - page 220

8.3.3 VNP-Inorganic Nanoparicle Complexes

A large variety of inorganic VNP hybrids have been developed, all of
which have potential for biomedical imaging applications and therapeutic
applications (this section and Section 8.4). To date, most of these materials
have been characterized biochemically and biophysically. Only a very few
examples describe an evaluation of the materials in cell culture

(see below).

In vivo data have not been reported yet.

As described in Chapter 5, the self-assembly mechanisms of VNPs or
VLPs can be exploited to encapsulate synthetic nanoparticles inside the
VNP or VLPs. The utility of SV40 VLPs-encapsulating QDs for live imaging
to follow virus internalization and trafficking has been demonstrated (Fig.
5.11) (Li

., 2009). The advantage of incorporating the imaging moieties
such as QDs on the inside of the VLP is that the exterior surface remains
unmodified. The exterior surface is involved in receptor recognition and
internalization so modifications can lead to abrogation of target specificity
and cell entry. This has been observed using a chemically engineered Ad
vector (Everts

et al

., 2006). Ad vectors were covalently modified with gold
nanoparticles; the goal was to engineer re-targeted gold nanoparticle-
modified Ads for a combination of hyperthermia treatment (cell killing
via heat) and gene therapy. Gold nanoparticles were attached using NHS
coupling to surface Lys side chains. Infectivity and efficient gene delivery
was only retained at low ratio labeling with gold nanoparticles. This,
however, limits the potential for efficient hyperthermia effects (Everts

et al

.,
2006). This strategy could be improved by fine-tuning and optimizing the
chemistry and testing various attachment sites or by incorporating the gold
nanoparticles into the interior of the vector (Everts

et al

., 2006).
In a different example, hybrid hydrogels consisting of M13 and gold
nanoparticles were investigated for cell sensing applications. Biocompatible
and tunable networks consisting of chimeric M13 particles displaying
cell-binding peptides and gold nanoparticles were formed on the basis of
electrostatic interactions. Cell binding and receptor-mediated internalization
of the phage particles, even when incorporated into the hybrid network,
were facilitated (Souza

et al

., 2007).
When developing hybrid systems that combine VNPs with synthetic
materials, it is important to re-evaluate the pharmacological and potential
toxic side effects. For example, recent biological studies revealed significant
cytotoxicity of QD nanocrystals (Portney & Ozkan, 2006). Similar data have
been reported for carbon nanotubes; because of their non-biodegradable
nature, cellular persistence and cytotoxic effects can occur with these
particles (Hardman, 2006; Prato

et al

., 2008). These
are important factors to be considered when working with VNP-inorganic
hybrids.

et al ., 2008; Takagi et al