VNPs as Tools for Nanomedicine - Viral Nanoparticles: Tools for Materials Science and Biomedicine - page 226

al ., 2006b; Pasqualini et al ., 1997; Souza et al ., 2006) (see also Section 8.6).

In vivo experiments using mice bearing human breast tumor xenografts

(axenograft is generated by transplanting tumor cells of a different species,
typically via subcutaneous injection into the flank of the animal) confirmed
tumor homing of M13 phages displaying the RGD motif (Pasqualini et al .,

1997).
The specific delivery of nanomaterials to sites of disease, such as cancer,
opens the door to the development of “smart” nanodevices for targeted drug
delivery (see below).

. therAPeutIC APProACheS

VNPs have been designed for therapeutic approaches such as the
delivery of drugs (chemotherapy). In addition, efforts have been made
toward alternative therapies including photothermal therapy (PTT)
and photodynamic therapy (PDT). PTT and PDT are closely related. In
PTT electromagnetic radiation, such as infrared, is applied to activate a
sensitizer, to release vibrational energy (i.e., heat) to kill the target cells. In
PDT, a photosoensitizer is excited with specific band light (or wavelength)
to generate reactive oxygen species to kill target cells. PTT and PDT can be
used for localized treatment. A limitation is that the treatment can only be
applied to the surface of tissues and is dependent on efficient penetration of
the radiation or light (Huang ., 2009).

A variety of strategies have been developed that allow generation of
hybrid VNP systems that are combined with synthetic materials such as iron
oxide, gold, and other metallic nanoparticles (recall Chapters 5 and 6), all of
which have potential for PTT or PDT. Evaluation of these materials

et al ., 2008; Ortel et al

in vitro

or has not been performed yet.

Besides using synthetic nanoparticles for such approaches, chemical
complexes such as ruthenium or fullerenes have also been shown to be
promising candidates for PDT applications. Derivatives of C

in vivo

(“Buckyball”)
have exceptional radical-scavenging properties and are as such good
candidates for use as photosensitizers in PDT. A major drawback of fullerene
material is its insolubility in aqueous solution. It was recently shown that
the solubility of C

60

can be significantly enhanced through conjugation
and multivalent display using CPMV VNPs or Q

60

VLPs. The VLP acts as a
hydrophilic carrier allowing cell delivery of the material. Biochemical and
biophysical data indicated multivalent display of around 40 C

b

molecules

60

per VNP. Indeed, studies confirmed the efficient delivery of the

hybrid material into cells (Fig. 8.9) (Steinmetz

in vitro

., 2009a). Whether
photodynamic cell killing can be achieved has not yet been demonstrated.

et al