Biomedical Engineering Reference
In-Depth Information
8.2.3 Gold NMs Toxicity
Gold is one of the inert metals possessing many applications that has been used
for centuries.
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During the past couple of decades, gold nanoparticles (AuNPs)
have been one of the most studied types of NPs for biomedical applications.
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A variety of methods have been developed for reproducible synthesis of gold to
produce a variety of morphologies with a narrow size distribution and precise
characteristics.
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Many of these properties are important for biomedical
applications including targeted drug and gene delivery,
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imaging diag-
nostics,
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or photothermal therapy.
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Gold nanorods have been applied to
imaging cancer
150
and tumor ablation.
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One of the drawbacks of the use of NMs in biological systems are the adsorp-
tion of proteins and nucleic acids onto the nanoparticle surface. NMs used for
targeted therapy depend on attached biomolecules with specific functions to
allow them to carry out their functions and most NPMs typically adsorb blood
serum proteins in an in vivo environment.
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Thus, a comprehensive under-
standing of protein binding, structure, and function as influenced by nanopar-
ticle characteristics including size, topography, crystal structure, and surface
chemistry is important in order to understand how the NMs affect cells, tissues,
organs, and organism.
A study reported by Gagner et al.
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investigated the effect of gold nano-
sphere (AuNS) and gold nanorod (AuNR) morphology on the adsorbed proteins
lysozyme (Lyz) and a-chymotrypsin (ChT). Both physical and spectroscopic
techniques were used to characterize the changes in protein structure and activ-
ity upon adsorption, as well as the stability and morphology of the protein-
nanoparticle conjugates. Their studies indicated that protein adsorption is
affected by the AuNP morphology. Both lysozyme and chymotrypsin adsorbed
to AuNPs with relatively low surface coverage with lysozyme forming a dense
protein layer on the surface of the nanorods.
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The lysozyme adsorption on the
AuNPs resulted in conformational changes that led to conjugate aggregation.
In a separate study, it has been reported that AuNPs can bind specifically
to heparin binding growth factors such as VEGF165 and bFGF, the two criti-
cal cytokines for the induction of angiogenesis, inhibit the cytokine activity in
vitro, and inhibit VEGF-induced angiogenesis in vivo
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but without toxicity
observed in the study. This finding indicates that AuNPs may be excellent NMs
for further modification and development of targeted drug or gene delivery.
Gold needs to be formulated to generate a common platform that can be modi-
fied easily to conjugate different molecules for drug or gene delivery.
The interaction of AuNPs with cells in vitro was evaluated using two can-
cer cell lines (human T-cell leukemia Jurkat and human pancreatic carcinoma
(PANC1)).
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AuNPs at of 10, 25, 50, and 100 nm in diameter at a constant
mass were exposed to the cells either in deionized (DI) water or in Dulbecco's
Modified Eagle's Media (DMEM) supplemented with fetal calf serum (FCS).
The zeta potential indicated that protein rich FCS increased the dispersion of
