Biomedical Engineering Reference
In-Depth Information
success is closely conditioned by their biodistributions, as they are intended to be administered
in vivo
by a general route of administration, that is, oral or IV. In turn, the expected biodistribution is espe-
cially closely conditioned to how nanoparticles interact with biological media, those found on their
way to their target sites from their sites of administration (Alexis et al., 2008; Owens and Peppas,
2006; Dobrovolskaia et al., 2008; Walczyk et al., 2010; Moyano and Rotello, 2011). Considering the
administration of a nanomedicine by the IV route, which is a typical route considered, immediate
interactions include the adsorption of proteins on the nanomaterial surface. A layer of proteins form
at the surface of the nanomedicine changing their “synthetic identity” into a “biological identity”
(Lynch et al., 2007; Dobrovolskaia et al., 2008; Norde, 2008; Walkey et al., 2012; Walkey and Chan,
2012). This event determines and regulates the subsequent biological response that will, in the end,
control the
in vivo
fate of the nanomedicine, including its eventual toxicity. Understanding the interac-
tions of nanomedicines with blood proteins is now considered to be a fundamental issue in predicting
and controlling their biodistribution and the eventual toxicological reaction they may induce (Lynch
et al., 2007; Walkey and Chan, 2012). While this is expected to provide for a better understanding on
how the physicochemical properties of nanomedicines that define their “synthetic identity” influence
the
in vivo
fate, it will enable a rational design of safe and efficient nanomedicines. Considering the
broader range of applications offered by nanotechnologies that far exceed that of nanomedicines, the
elucidation of interactions occurring between nanomaterials and proteins is expected to contribute to
evaluating and elucidating health and environmental risks which may arise from their use in various
domains of the industry and in consumer products distributed on a large scale.
Investigating the interactions of proteins with nanomaterials is a complex task. Nanomaterials
occur with various compositions, sizes, shapes, and surface properties (Algar et al., 2011; Etheridge
et al., 2013; Lehner et al., 2013). A glance at this complexity is provided by considering the nature
of the components that compose nanomaterials developed as nanomedicines; these include lipids,
polymers, carbon, and metal for the simpler systems. More complex systems are composites resulting
from the association of metal colloids and lipids or polymers for instance. A second difficulty arises
from the large numbers of proteins that are found in the blood and the broad range of concentrations
in which they individually occur. There are over a thousand different proteins with differences in
concentrations spread over 10 orders of magnitude (Anderson et al., 2004). Additionally, the adsorp-
tion of protein on a surface of a material is kinetically dependant and the composition of the adsorbed
proteins evolves with time (Hirsh et al., 2013). Finally, investigating interactions of proteins with
nanomaterials is not simply an extension of approaches applied to biomaterials. The range of nano-
material sizes imposed the development of specific methods. Some were adapted from those used to
evaluate biomaterials, but a lot needed to be developed specifically to be applied to nanomaterials
(Lynch et al., 2007; Vauthier et al., 2009, 2011; Walkey and Chan, 2012; Welsch et al., 2013).
Research carried out on the interactions of nanoparticles with proteins has been intensified over
the last two decades. They started soon after it was assumed that proteins play a fundamental role
in defining the
in vivo
fate of nanomaterials, including those designed as drug carriers. Today, it is
expected that the biodistribution of nanomaterials may be anticipated from the type of proteins that
are adsorbed onto their surface. It is also assumed that it may be possible to target a nanomaterial
to a specific site in the organism, taking advantage of a preferential adsorption of a certain plasma
protein—if it exists—and to the specific design of the nanomaterial. While taking advantage of the
preferential adsorption of proteins may be a strategy to conceive targeted nanoparticles for drug
delivery, a systematic identification of proteins that adsorb onto nanomaterials could be used as a
method to identify preferential sites of accumulation in the body for the purpose of anticipating the
safety of a nanomaterial. Methods of camouflaging the surface of nanoparticles were developed in
parallel to research carried out to decrypt the types of proteins adsorbing onto a nanoparticles sur-
face. To this purpose, PEG was chosen because of its known antifouling properties from its uses to
improve the resistance to the protein adsorption of biomaterials (Jeon and Andrade, 1991; Jeon et al.,
1991; Gref et al., 1994; Papahadjopoulos et al., 1991; Banerjee et al., 2011). Together with obser-
vations of the occurrence of protein adsorption modifications, the addition of PEG at the surface
