Essay Writing Service

Gold Nanorods (GNRs) – Surface chemistry, Size and Shape: Effects on Biological Applications

do not necessarily reflect the views of

Gold Nanorods (GNRs) – Surface chemistry, size and shape: effects on biological applications


In the ever-advancing field of nanotechnology and materials science there has been a buzz in the air in recent years over Gold Nanorods (GNRs). Their unique structure and ease of synthesis provides a range of optical properties that can be readily manipulated. These properties can be utilised in various applications such as surface functionalisation, photothermal therapy to manage tumours and cancer cells. In this review, we will look at the current research that analyses the toxicity of GNRs and what effects the surface chemistry and synthesis have on this. We will also discuss what effect the size and shape of GNRs have on biological systems, reinforcing why they are making such a statement in the world of science.

Gold Nanorods (GNRs) in recent years have been the focus of many studies that consider their various biological applications. One of the major properties of GNPs that have placed them into the spotlight is their extremely high surface to volume ratio. The surface-volume ratio provides the opportunity for even the smallest GNPs to attach a very diverse range of biomacromolecules in high concentrations [1].
Along with the high surface-volume ratio that all GNPs exhibit, GNRs have unique optical properties due to surface plasmon resonance (SPR). SPR occurs due to the collective oscillation of electrons on the surface of the GNRs at specific wavelengths [2]. Gold nanorods exhibit strong scattering and absorption intensity at the near infrared range, making them the nanoparticle of choice for biomedical applications such as tumour targeting. The seed-mediated growth method in which GNRs are synthesised is a very common process. This makes GNRs easily accessible and readily available.
Due to the spotlight that GNPs have had, it is important to understand how their surface chemistry can influence their interactions with biological systems. In the literature there has been an observed correlation between the surface chemistry of GNPs and how this dictates their biological behaviour [3]. More specifically how their surface chemistry alters their cytotoxicity [4-6].

Gold nanorod (GNR) synthesis requires the surfactant cetyltrimethylammonium bromide (CTAB) [7], this process produces a high yield of GNRs with surface plasmon resonances in the infra-red as well as visible light range. CTAB is the agent that drives anisotropic growth as well as provides the stabilization needed to form the bilayers on the GNRs [8]. Quite a significant amount of CTAB is used in this synthesis and after the synthesis there is still an amount of CTAB remaining on the surface of the GNRs [9]. The excess CTAB on the surface has both a lack of stability in biological systems and presents a significant amount of cytotoxicity [3, 10, 11]. In the literature it has presented that GNR solutions that are CTAB-capped at a certain concentration present a substantial amount of cytotoxicity at around 70% loss of cell viability [10]. In this paper published by Wiley, with over 600 citations was an extraordinary paper. It was well constructed and no faults could be found with it. With that amount of citations, it has clearly influenced the further investigation of the cytotoxicity of GNRs. Now we have identified that CTAB is the problem, how have researchers attempted to solve it? You’re probably thinking, remove the CTAB, which is a very reasonable suggestion. Removing the CTAB from the surface of the GNRs and replacing them with other viable biomolecules is not a simple process. By removing the CTAB from the surface of the GNRs the first issue encountered is the uncontrollable aggregation of the GNRs. What was found was that the toxicity was not caused by the CTAB that was bounded statically to the surface of the GNRs as Connor, 2005 [12] had reported quantitatively. In this research is was reported that 1µm of passivated CTAB nanoparticles after three cycles of centrifugation did not display any indications of cytotoxicity to cultivated cells. The unbound CTAB was in fact the culprit of the cytotoxicity of the cultivated cells. Therefore to reduce the cytotoxicity of GNRs, the excess CTAB should be removed by repeated centrifugation as several studies have shown [13]. While centrifugation has shown to remove the excess CTAB, the CTAB bilayers are still present on the surface of the GNR. These bilayers could be removed by being desorbed, though that would cause aggregation of the GNRs.
A lot of research in the past decade has considered the surface modification of GNRs to try and overcome the issues stated above. Surface functionalisation provides the potential to reduce the cytotoxicity of the GNRs as well as improve its stability, solubility whilst retaining its optical properties. For example polyamidoamine (PAMAM) has been used to modify GNRs and was found to decrease and increase the cytoxocity and biocompatibility respectively [14].

To reduce the toxicity of the GNRs and improve their biocompatibility there have been several ligands that have been proposed to cover or ‘cloak’ the GNRs. The three methods I will be investigating are Polyethylene glycol (PEG) coated GNRs, Silica-coated GNRs and Lipid-GNR composites.

Amorphous silica nanoparticles have the potential to become compatible with biomolecules using either electrostatic interaction or physical absorption as shown by Zhang, J.-J., Y.-G. Liu, L.-P. Jiang, and J.-J. Zhu, 2008 [11]. The two main characteristics to silica coatings that are their ability to prevent the aggregation of GNRs and adjusting the thickness of the silica shell can alter the optical characteristics of the GNR. Zhang, J and team utilised seed-mediated methods to synthesise GNRs. TEOS polymerisation was used so surround the GNR core with a silica layer. The results of this study showed that the nanocomposites had both good solubility and compatibility which was found useful for Hb immobilisation. There was no loss in biological activity and maintained its high stability. This was a very well written study that supported that silica coating can indeed reduce the toxicity of GNRs.
Further supporting studies by Cong, H., R. Toftegaard, J. Arnbjerg, and P.R. Ogilby, 2009 [15] showed that there was a proven difficulty in synthesising a uniform silica layer over the GNRs, which is important as this may alter their optical properties. The cause of this was found to be an excess of CTAB in high concentrations, confirming the results of the Wiley published study mentioned earlier. In this study, they established that if the CTAB could be removed, a uniform silica layer could be formed. Further, Chen, Y.-S., W. Frey, S. Kim, K. Homan, P. Kruizinga, K. Sokolov, and S. Emelianov, 2010 [16]   used mPEG-thiol instead of CTAB. From this a silica shell with mPEG polymer was formed. They found that by mediating the amount of TEOS, produced GNRs with shells of differing thickness. This further probed the study and further analysis was made using multilayer nanorods with gold-silica-gold architecture. These nanorods have unique optical properties and by altering the thickness of each of these layers can provide a flexible surface resonance. It was very promising to see studies providing similar results, further probing discussion on the topic.
Silica coated GNRs have various biomedical uses such as medical imaging. They can connect with DNA as shown in the literature for enhanced surface plasmin resonance imaging (SPRI). DNA coated GNRs have been shown to display a strong absorption band around 780nm which is used to stimulate the sensitivity of SPRI measurements [17]. This is just one example of the promising uses of the coated GNRs in biological applications.
PEG modification has been used to enhance GNRs in previous studies as such by Niidome, T., M. Yamagata, Y. Okamoto, Y. Akiyama, H. Takahashi, T. Kawano, Y. Katayama, and Y. Niidome, 2006 [18]. In this study mPEG-SH was added to the CTAB solution during the synthesis of the GNRs and the excess CTAB was removed via dialysis. The GNRs were then checked to make sure they were PEG-modified by measuring the zeta potentials which decreased significantly to the neural level. The results from this study demonstrated that the GNRs were in fact PEG modified and exhibited low cytotoxicity. It was important to note that in this study the PEG-GNRs were also stable whilst in blood circulation with a half-life of up to 1hr on average. There was also no accumulation in any of the major organs for except for the kidneys for the first 72 hrs. This study was vital in being able to stabilise the GNRs in physiological conditions as it demonstrated promise for GNRs to be used in biological applications. This was an incredible research paper that has been cited well over 900 times the last 10 years. Although it is quite old, with an impact factor of 7.7, the journal of controlled release is very influential. To further validate this study Huang, H.-C., K. Rege, and J.J. Heys, 2010 [19] also used PEG-GNRs and showed that the GNRs could be maintained in extra cellular space, this could lead to further research into inducing cell death in cancer cells. Niidome, T again  4 years after the previous PEG modification study cited earlier successfully synthesised biocompatible PEG-GNRs and used them for photothermal cancer therapy [20]. What was recorded was the growth of the tumour in mice after a treatment. What the results showed was the mice treated with both the direct injection of PEG-GNRs and irradiation of laser light displayed a substantial suppression of the tumour. The control mice on the other hand treated with either the PEG-GNRs or the laser did not show any differences on tumour growth compared to the non-treated mice. This is an interesting point which will stimulate further research into why the combination of the PEG-GNRs and laser irradiance provided the desired results. These successful PEG studies, over a 5-year period reinforced each other, concluding each time that the PEG coatings can in fact reduce the cytotoxicity of GNRs. I believe this consistency is very important for the further development of GNRs in studies to come.

The simple attachment of lipid bilayers onto solid surfaces is a promising topic. Recent studies have been zeroing in on the attachment of lipid bilayers and nanomaterials for biological applications. Lipid bilayers have been shown to effortlessly interact with hydrophilic surfaces such as silicon and glass, which enables an almost perfect coating [21]. These properties have stimulated current Research supporting that lipid bilayers can be formed on gold with the aid of an amphipathic α-helical viral peptide [22].
Phosphatidylcholine (PC) was proved in the literature to control the aggregation of GNRs [23]. In this study, CTAB was removed from the GNR solution and placed into a chloroform phase containing PC. The now PC-GNRs were shown to have low cytotoxicity as PC is not at all toxic to living cells.
More recently, a reverse micelle based polyacrylate coating method was undertaken to obtain various functional nanorods [24]. The micelle based coating was shown to be very versatile as the coating produced water soluble GNRs without particle aggregation. This coating developed could absorb a variety of functional groups including primary amines, ethylene glycol and fluorescein. This makes them much more suited for biomedical applications. This more recent study, although not highly cited does make progress in the GNR uses in biomedical applications and I believe should stimulate further investigation for this technique.
Research conducted by Castellana and team in 2011, studied the label-free biosensing with lipid-functionalised GNRs [25]. Thiol-gold linkages were used to tether the GNRs and lipids. They made use of the lipid coated GNR biosensor to detect membrane-active drugs.  The study made a large step in the potential for lipid-coated GNRs to be used in biosensors and ties in perfectly with the continuous improvement of lipid GNRs in biomedical applications.

It is clear he PEG, silica and lipid-coatings were shown in the literature to have reduced the cytotoxicity and increased the biocompatibility of the GNRs. Multiple papers supported this.

Now we have seen how the  surface chemistry of GNRs can influence their use in biological applications, what size GNR is optimal and what applications can utilise this?

GNRs very unique plasmonic properties can be employed in photothermal therapy. Photothermal therapy is the excitation of the conduction electrons of the gold. Through the excitation of surface electrons heat is produced that can be transferred to the surrounding environment [26]. The plasmonic photothermal therapy of cancer is one of the major applications of this localised heat transfer [27]. In order to target cancerous cells and tumours below the skins surface, near infrared external radiation is the most appropriate method of doing so as it can penetrate up to 10cm into soft tissue [28]. As we know from earlier, altering the size of the silica coatings on GNRs can achieve this. This is exactly what Shen and co-workers [29] did in 2013. They found that the silica-coated GNRs had both a significant potential in both photothermal therapy and drug delivery to tumorigenic regions.  Of all the shapes of Gold nanoparticles, GNRs present the most ideal Near Infrared absorption cross section [30] and the highest thermal transmission efficiency [31].  Mackey, M.A and co-workers [32] did research determining what the most effective size of GNRs are for use in thermal phototherapy. They did this by comparing the plasmonic properties and efficiency of GNRs as photothermal contrast agents for three different size GNRs. The three-different size GNRs used were 38x11nm, 28x8nm and 17x5nm. What the results of the study showed was that the 28x8nm GNRs were the most efficient in plasmonic photothermal heat generation. This probed further analysis using in vitro experiments. This experiment compared the same three size GNRs and their ablation of human oral squamous cell carcinoma. The 28x8nm GNR was the most effective size nanorod. This size GNR displayed the best compromise between the absorption of Near infrared radiation and the size of the electromagnetic field around it. This sized nanorod had an electromagnetic field that extended far enough from the particle surface to the target cells to allow for field coupling. Whereas the larger GNRs showed to scatter too much of the energy rather than absorb it and the smaller GNRs did not have an EM field that penetrated far enough to heat the surrounding area. These properties of the 28nm GNR attributed to absorption which displayed the lowest cell viability after a 2 minute exposure. This was a very well written research paper that had plenty of background information explaining the purpose of the study. It utilised proven methodology such as the seed mediated method for synthesizing the GNRs and had a logical flow. It was sourced from the Journal of Physical Chemistry B, although this is a peer reviewed journal I believe it provides the opportunity for upcoming researchers to reach out to an audience. The paper had received 109 cites since 2012 which is very promising. I do believe it will stimulate further development in this field of nanotechnology.


As you can see it is clearly evident that GNRs have the promise of being commercially viable in biological applications. The seed mediated growth has shown to have its contributions to the cytotoxicity of GNRs, restricting its potential biocompatibility. From this review of the literature we have analysed the different methods used to overcome the toxicity caused by CTAB and improve the properties of GNRs for biological applications. Each of the methods used has their own respective benefits. Silica coated GNRs can enhance the biocompatibility, the PEGylation of GNRs allowed the bioconjugation of the GNRs and transforming into well-ordered films [33]. The lipid-coated GNRs also showed promise for increasing the functionality of GNRs in biological systems through the swapping of biocompatible functional groups on the GNR surface. All these methods not only solved the CTAB-toxicity issue, they also provided a range of techniques to optimise the surface functionalisation of GNRs.
The studies determining the optimal size of the nanorods, showed in vivo that GNRs do indeed have the potential to be used commercially in cell targeting roles. These unique properties of GNRs make them promising nanotechnologies for biological applications.


With Our Resume Writing Help, You Will Land Your Dream Job
Resume Writing Service, Resume101
Trust your assignments to an essay writing service with the fastest delivery time and fully original content.
Essay Writing Service, EssayPro
Nowadays, the PaperHelp website is a place where you can easily find fast and effective solutions to virtually all academic needs
Universal Writing Solution, PaperHelp
Professional Custom
Professional Custom Essay Writing Services
In need of qualified essay help online or professional assistance with your research paper?
Browsing the web for a reliable custom writing service to give you a hand with college assignment?
Out of time and require quick and moreover effective support with your term paper or dissertation?