Biomedical Engineering Reference
In-Depth Information
of nanomaterials could modulate the pharmacokinetic and biodistribution of the corresponding
nanoparticles (Gref et al., 1997, 2000; Peracchia et al., 1999; Vonarbourg et al., 2006, see for review
Li and Huang, 2008). However, the use of PEG presents some limitations, following observations
from clinicians, while the use of PEGylated nanomedicines was intensified in human medicine.
The most serious concern is the appearance of a new type of toxicity that occurs as a hypersensitive
reaction called C activation-related pseudoallergy (CARPA) (Jiskoot et al., 2009; Szebeni et al.,
2011; Lehner et al., 2013). Only few works have considered the use of alternative polymers to PEG
to modulate the surface properties of nanoparticles in the aim to modify protein adsorption. The
few numbers of polymers used in this purpose included polyoxazolines, oligo- and polysaccharides,
polyelectrolytes, and zwitterionic polymers (Passirani et al., 1999; Chauvierre et al., 2003; Labarre
et al., 2005; Lemarchand et al., 2004; Estephan et al., 2010; Walkey and Chan, 2012; Welsch et al.,
2013). Whatever the approach used to modify surface properties of nanoparticles, the control of
the
in vivo
fate of nanomedicine from the protein adsorption pattern needs the understanding of
the relationship between the synthetic identity of the nanomaterials, its biological identity, and the
corresponding physiological response. Each can be described by many parameters that consider-
ably increase the challenge. We should admit that we are still at the beginning. Nevertheless, a few
general principles have emerged from the number of studies available in literature. For instance,
Walkey and Chan (2012) have provided a comprehensive analysis of data collected from many
of these works. They described an “adsorbome” of 125 plasma proteins for nanoparticles of var-
ious compositions and surface properties. From this analysis, they draw a relation between the
physicochemical characteristics of the nanoparticles and the corresponding absorbome. The dif-
ficulty of this work came from the various sources of data, hence the wide range of nanoparticles.
Unfortunately, this analysis could obviously not be based on standardized evaluations of nanomate-
rial properties and of protein adsorption. In agreement with the authors' findings, this would be the
main restriction of this work. Nevertheless, such an analysis deserves respect and will be very use-
ful in the future. The conclusion that came out of this work was that 2-6 proteins from the plasma
predominantly adsorbed on the surface of a nanomaterial together with many more that adsorbed
at a lower abundance. Another remarkable analysis was provided by Walkey et al. (2012) consider-
ing a series of PEGylated gold nanoparticles and investigating, in parallel, their “absorbome” and
their uptake by macrophages. It also emerged from the work done that PEG chains grafted at the
surface of nanoparticles control the adsorption of proteins by a steric effect (Gref et al., 2000; for
other references, see Owens and Peppas, 2006; Alexis et al., 2008; Walkey et al., 2011). The use of
polyelectrolytes as nanoparticle coating materials leads to a different mechanism of control of the
adsorption of proteins on the nanoparticle surface. In this case, proteins were found to behave like
multicounterions that can interact with the charge of polyelectrolytes via the patches of opposite
charges they display on their surface (Ballauff and Borisov, 2006; Ballauff, 2007; Welsch et al.,
2013). In our group, we have started investigating the interactions of proteins with polysaccharide-
coated poly(alkylcyanoacrylate) (PACA) nanoparticles. These nanoparticles have the potential to
improve the delivery of many types of drugs (Vauthier et al., 2007; Andrieux and Couvreur 2009;
Nicolas and Couvreur, 2009). They can be obtained with various surface properties, thanks to their
method of preparation and the large panel of polysaccharides that can be used as coating materials
(Nicolas and Vauthier, 2011). The aim of this chapter was to propose a comprehensive review of our
contribution to the understanding of the influences of nanoparticle properties on interactions with
plasma proteins. In the first part, we summarize the characteristics of a series of polysaccharide-
coated PACA nanoparticles that were synthesized to carry on our work. Results from the interac-
tions of proteins with nanoparticles are presented in the second part of the chapter. As it will be
explained, models drawn to describe the “synthetic identity” of several nanoparticles could be used
to elucidate the mechanisms controlling the accessibility of proteins to the nanoparticle surface
during protein adsorption. It also serves to understand the mechanisms beyond the capacity of the
nanoparticles to trigger the activation of proteins involved in the immune system, which play a fun-
damental role to define the
in vivo
fate of IV injected nanoparticles.
