VNPs as Tools for Nanomedicine - Viral Nanoparticles: Tools for Materials Science and Biomedicine - page 208

part of the reticuloendothelial system (RES), which is a component of the
immune system. Its function is to remove antigens, such as proteinaceous
nanoparticle structures, from circulation (Peiser

., 2002).
A potential advantage of plant VNPs over synthetic nanomaterials is that
plant VNPs could be administered as edible vaccines or therapeutics. Plant
VNPs are robust and can withstand harsh conditions. It has been shown
that CPMV particles remain structurally sound under simulated gastric
or intestinal conditions (simulated gastric or intestinal fluids containing
proteases and acidic pH values of 2-6) (Rae

et al

., 2005). Furthermore, CPMV
particles have been shown to be bioavailable following oral administration
in mice (Gonzalez

et al

., 2005).
Pharmacokinetic properties are highly dependent on surface charge and
materials properties (reviewed in Li & Huang, 2008). The more positive
the surface charge of a nanoparticle, the longer its plasma circulation time.
This holds true for VNPs: the negatively charged VNPs CPMV and CCMV, for
example, have rather short plasma circulation times of

et al ., 2009; Rae et al

t < 15 min (Kaiser

1/2

b

et al ., 2007; Singh et al ., 2007), whereas positively charged Q particles

reach plasma half-life times of greater than 3 h (Prasuhn ., 2008). CPMV

and CCMV particles display negative surface charges of −180e and −120e,
respectively. In stark contrast, Q

et al

b

particles have a positive surface charge
of +300e [values are derived from the Virus Particle Explorer Database
(VIPERdb); http://viperdb.scripps.edu].
VNPs with altered surface charges were compared, where surface
charge alteration was accomplished using chemical or genetic modification
methods. Data obtained with each platform tested, Q

b λ

and M13,
were in good agreement: the more positively charged the VNP, the longer its
circulation time (Molenaar

, phage,

1

et al ., 2002; Prasuhn et al ., 2008; Srivastava et al .,

b

2004; Vitiello particles

remained circulating in plasma for several hours. Chemical modification
at solvent-exposed, positively charged Lys side chains increased the net
negative charge and greatly reduced plasma half-lives (Molenaar

et al ., 2005). For example, non-modified M13 and Q

et al .,

2002; Prasuhn ., 2008). Many modification chemistries involve the

covalent modification of Lys side chains on the surface of VNPs, and thus
may alter the surface charge. This of course depends on the ligand attached;
if a neutral or negatively charged molecule is attached to a Lys side chain,
the overall surface charge of the VNP is expected to be more negative,
thus leading to shorter circulation times. However, if a positively charged
molecule is covalently linked to surface Lys residues, the overall surface

et al

1

7 symmetry
[Database of the International Committee on taxonomy on Viruses (ICTV); http://www.ncbi.
nlm.nih.gov/ICTVdb].

λ phage is a DNA-containing coliphage with a head-tail structure; the head has T =