Angewandte
Chemie
DOI: 10.1002/anie.201404100
Bio-Nanomaterials
Polyvinyl Alcohol as a Biocompatible Alternative for the Passivation of
Gold Nanorods**
Calum Kinnear, David Burnand, Martin J. D. Clift, Andreas F. M. Kilbinger,
Barbara Rothen-Rutishauser, and Alke Petri-Fink*
Abstract: The functionalization of gold nanorods (GNRs)
with polymers is essential for both their colloidal stability and
biocompatibility. However, a bilayer of the toxic cationic
surfactant cetyl trimethylammonium bromide (CTAB) ad-
sorbed on the nanorods complicates this process. Herein, we
report on a strategy for the biocompatible functionalization of
GNRs with a hydrophobic polymeric precursor, polyvinyl
acetate, which is then transformed into its hydrophilic ana-
logue, polyvinyl alcohol. This polymer was chosen due to its
well-established biocompatibility, tunable “stealth” properties,
tunable hydrophobicity, and high degree of functionality. The
biocompatibility of the functionalized GNRs was tested by
exposing them to primary human blood monocyte derived
macrophages; the advantages of tunable hydrophobicity were
demonstrated with the long-term stable encapsulation of
a model hydrophobic drug molecule.
which is polyethylene glycol (PEG). In a number of other
reports either a monomer similar to CTAB was polymerized
within the surfactant bilayer,[4] or the CTAB was overcoated
with biocompatible polyelectrolytes or amphiphilic polymers
such as polyvinylpyrrolidone; however, these reports are few
and far between.[5] One reason for the ubiquity of PEG in
functionalizing GNRs could be due to its amphiphilic nature,
which enables easier penetration through the CTAB bilayer
and subsequent grafting to the gold surface with a terminal
thiol group. Nevertheless, we have previously shown that the
often simple functionalization with thiolated PEG, that is,
simply mixing and waiting, is not sufficient especially at low
PEG concentrations; ligand exchange occurs in two different
stages with the first occurring at the ends of the nanorods
before the near-complete surface coverage.[6]
It is essential that alternative polymers are available for
passivating the surface of GNRs. This is due to a number of
known limitations, four of which we highlight here. Firstly, the
PEG coating of “stealth” liposomes has been indicated to
cause drug leakage[7] and induce immunogenic responses
through complement activation.[8] Secondly, studies have
found anti-PEG antibodies in a population of healthy
humans; exposure was likely due to the increased use of
PEG in pharmaceutical formulations, food products, and
cosmetics.[9] These antibodies caused a reduction in the
circulation time of PEGylated agents in vivo and accelerated
blood clearance upon repeated administration.[10] Thirdly,
PEG is known to impart “stealth” properties to NPs, which is
potentially undesirable if there is a specific biological target
such as the immune system.[11] Finally, there is an ongoing
discussion about the significance of tumor targeting via leaky
vasculature with “stealth” NPs, as well as the potential side
effects of having prolonged exposure to cytotoxic compounds
in the blood.[12] In addition to the above limitations, conven-
tional PEG has a low degree of functionality: often only the
end group is reactive and therefore further synthetic steps are
needed to introduce higher numbers of functional moieties
such as dyes or targeting peptides.
T
he great attraction of GNRs stems from their fascinating
optical and electrical properties, which are often simply tuned
through their size or aspect ratio.[1] With control of these
dimensions as a goal, vast improvements have been made
over the past 10 years in the reliability of the synthesis leading
to monodisperse GNRs and shape yields of close to 100%.[2]
As with most nanoparticles (NPs), before use in the desired
application, they must first be functionalized with, for
example, targeting ligands, inorganic shells, and stabilizing
polymers. However, the case of GNRs is notably more
complex than that of their spherical analogues, primarily due
to the cytotoxic surfactant used and the two distinct surface
curvatures at the ends and the sides.[3] Crucially, this
surfactant is present as a partially interdigitated bilayer that
complicates the functionalization due to the rapid loss of
colloidal stability upon destabilization of the bilayer.
Despite the explosion of publications on GNRs (over 7000
from 2002 to 2012 according to the ISI Web of Knowledge),
there is typically one polymer used to detoxify the suspension,
[*] C. Kinnear, D. Burnand, Dr. M. J. D. Clift, Prof. A. F. M. Kilbinger,
Prof. B. Rothen-Rutishauser, Prof. A. Petri-Fink
Adolphe Merkle Institut, Universitꢀt Freiburg
1723 Marly (Switzerland)
It is clear that the ability to test and use alternative
polymers is severely hindered by the difficulty of functional-
izing GNRs. In order to expand and complement this limited
range of biocompatible polymers, we chose to investigate the
case of polyvinyl alcohol (PVA). This polymer presents
excellent biocompatibility, “stealth” properties dependent on
molecular weight, a high degree of hydrophilicity, and tunable
hydrophobicity.[13] The combination of these properties along
with the FDA approval of PVA in food, pharmaceuticals, and
implants such as stents, makes PVA an attractive candidate
for GNR functionalization.
E-mail: alke.fink@unifr.ch
C. Kinnear, D. Burnand, Prof. A. F. M. Kilbinger, Prof. A. Petri-Fink
Department Chemie, Universitꢀt Freiburg
1700 Freiburg (Switzerland)
[**] This work was supported by the Swiss National Science Foundation
(PP00P2_123373), the Adolphe Merkle Institute, and FriMat.
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2014, 53, 1 – 6
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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These are not the final page numbers!