1. Gold Nanorods/Nanoparticles: Mechanisms, Application and Toxicity
Casey Karler, George Ryan, Kirsten Sochinski

2. Introduction: Materials Science Background
Materials science is a rapidly-growing field of science in today’s industry
In the journey to find remedies for complicated diseases like cancer, materials science can offer potential solutions via nanoparticles
In addition to medicine, nanoparticles are promising for applications in other areas like catalysis, energetics, and electronics
As with any emerging technology, there are drawbacks, and this includes biological toxicity for some nanoparticles
This presentation will cover the chemical mechanisms of gold nanoparticles, biological applications, and potential toxicity in the context of medicinal use

3. Background: Materials Science
Nanoparticles are small particles less than 1 micrometer in size, that are often composed of multiple layers of atoms/compounds
Nanoparticle crystal structures often display altered or better optical properties than the normal material, due to better energy transfer and more consistency
Nanorods, specifically, can transmit different visible light wavelengths depending on their aspect ratio (length and width)

4. Background: Materials Synthesis
Gold nanorods can often be easily synthesized with a low cost of reactants and high precision
They can be created through certain reactant ligands (CTAB) binding the sides of the growing structure with more strength
This forces additional gold particles to grow on both ends instead of the sides, creating rods
Rod shape/size can be tuned by changing reaction conditions (reactant concentrations, temperature, stirring, time)
Surfactants (soap like molecules) such as CTAB are essential for the synthesis of uniform nanorods

5. Common gold nanoparticle morphologies
Gold nanorods
Faceted gold nanoparticles
Gold nanostars
Gold nanocubes

6. Significance: Gold nanorods
Different shapes of rods transmit different specific wavelengths of visible light, which is useful for many unique applications
The images to the right demonstrate how the nanorod length determines the transmitted colors
This is important because some applications require specific optical properties
Longer rods = more red color

7. Biological Applications: Nanoparticle Shapes
Nanoparticles of a specific size or shape can be used for many applications in fields of medicine, including near infrared imaging (NIR)
Various gold nanoparticle shapes can be intravenously injected for cancer therapies, such as:
Nanospheres: for tumour imaging (enhanced radiative property; NIR), Photothermal therapy (enhanced radiative property; NIR) and drug therapy in cancers such as:
Ovarian carcinoma
Nanorods: for cell imaging (visible lights), photothermal therapy and drug therapy in cancers such as:
Adenocarcinoma, breast cancer and melanoma
Nanoshells: for tumour imaging (enhanced radiative property; NIR), Photothermal therapy (enhanced radiative property; NIR), drug therapy and photodynamic therapy in cancers such as:
Liver cancer and Glioblastoma

8. Biological Applications: Cancer Therapy
Gold nanoparticles have been shown to be effective in cancer therapies since they have theranostic properties
Theranostics: When a material, such as a gold nanoparticle (AuNP) can be used for high resolution/contrast imaging for tumors while concurrently delivering therapeutic effects directly to the tumor cell
Molecular imaging can be used to help visualize and characterize tumor cell types
Therapeutic effects can involve direct tumor cell death through heat or actual nanoparticle-cell binding
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9. Biological Applications: Cancer Therapy Types
Photodynamic therapy: is a cancer treatment utilizing therapeutic agents with light and oxygen to kill cancer cells
Photothermal therapy: when a therapeutic agent is excited by light to create heat that will subsequently kill the cancer cells
When using thermal therapy, it is ideal to use therapeutic agent in the near-infrared (NIR) region for radiation to reduce that amount of heat that could potentially kill other normal cells
Deep set tumors need very weak absorption properties to ensure that radiation therapy does not damage other vital organs
( effects/treatment-types/photodynamic-therapy.html)

10. How do nanoparticles bind to the correct cells?
In order for gold nanoparticles to reach the desired tumour cells, they are conjugated with antibodies that have an affinity for epidermal growth factor receptors (EGFR’s), since these are commonly found in cancer cells
Utilization of antibodies helps guide researchers to tumour sites
With certain wavelengths, detection of the tumour-antibody complex creates a vivid image of the tumour to use photothermal or photodynamic therapy to induce cell death
Having accurate imaging with the use of antibodies ensures minimal use of photothermal therapy or photodynamic therapy

11. Biological Applications: Gold Nanorods
The cancer applications of particles such as gold nanorods are thought to extend further than their optical and energetic properties
This is because of the fact that the aspect ratio (length and width) of nanorods can be tuned to very specific dimensions in the synthesis process
A particle of the correct size can make its way into tumor orifices that have sizes unique to that tumor cell; this is one mechanism by which the particles can accumulate in tumors, rather than normal tissue types
Particles that have accumulated in tumours can be used for tumour cell location or induced cell death via photodynamic/photothermal therapy

12. Toxicity concerns with gold nanorods used for cancer therapy
Medicinal nanorods have significant potential for guidance and diagnoses of human diseases. However, the potential for adverse effects is a risk that still warrants further investigation
While most gold nanorods have shown no adverse effects on their own, the CTAB (cetyltrimethylammonium bromide) needed to synthesize them has been investigated for its potentially toxic effects
In efforts to reduce toxicity, researchers are looking to purify or reduce the toxicity of the free CTAB by coating the particles in polyelectrolyte shells, or by using free radicals. However, these methods are still being under development

13. How are gold nanorod toxicity levels measured?
In vitro, there are various factors that need to be accounted for when it comes to cellular health; this process is similar to processes used for drug development screening criteria.
LDH assay: looks at cellular damage by release of lactic acid
MTT assay: looks for disruption of metabolic processes
ROS assay: Looks for oxidative stress

14. The nano debate….
Although progress has been made in the area of biological nanoparticle research over the last couple decades, questions remain concerning the fundamental characteristics of nanorods and their interactions with biological environments
Various experimental techniques have been implemented to determine if gold nanorods and their components are heavily toxic
An MTT assay was used to determine that nanorods had no pertinent metabolic effects on the cell, nor did they cause any phenotypic changes
Another study found that excess administration of nanorods at precisely 2nm in length will covalently interact with cell membranes which will then lead to apoptosis (similar to the interaction of PLA2 proteins from snake venom that we discussed in class)
Researchers are currently working on

15. CTAB toxicity in cells
Research pertaining to CTAB toxicity to cells is ongoing
There are two theories that suggest why CTAB can induce cell death
CTAB interacts with and destabilizes the phospholipid bilayer, resulting in apoptosis
CTAB dissociates into a CTA+ ion, which will bind to ATP synthase. This results in energy depletion for the cell

16. Gold nanorods in vivo
Currently, tests to determine toxicity are being conducted pertaining to nanorods, and these tests are looking for toxicity to specific tissues
The studied effects include nephrotoxicity, hepatotoxicity, immunogenic toxicity, oxidative stress, and hematological toxicity
Another in vivo experiment looked into nanorod distribution throughout the body, as well as nanorod removal once they are no longer needed

17. Conclusions
Materials science and nanotechnology are rapidly emerging fields of science, and new synthesis methods are constantly being developed that yield uniform nanoparticles with very specific dimensions and properties
Gold nanorods/nanoparticles are desired for their unique optical and energetic properties
Particles like gold nanorods offer very real and promising solutions to a wide array of biological applications, in addition to their known other inorganic catalytic applications
Gold nanorods appear to be ideal for applications in biological imaging, photodynamic therapy, and photothermal therapy
Although gold nanorods are promising, potential toxicity of the rods themselves or reactants needed to synthesize them require further investigation

18. Works Cited Primary sources
Guo, J., et. al. (2017). Gold nanoparticles enlighten the future of cancer theranostics. International Journal of Nanomedicine. (12) doi: /ijn.s140772
Perez-Juste, J., et. al. (2005). Gold nanorods: Synthesis, characterization and applications. Coordination Chemistry Reviews, 249(17- 18), doi: /j.ccr
Alkilany, A. M., & Murphy, C. J. (2010). Toxicity and cellular uptake of gold nanoparticles: What we have learned so far? Journal of Nanoparticle Research, 12(7), doi: /s
Au, L., et. al. (2009). Quantifying the Cellular Uptake of Antibody-Conjugated Au Nanocages by Two-Photon Microscopy and Inductively Coupled Plasma Mass Spectrometry. ACS Nano, 4(1), doi: /nn901392m
Huang, X., et. al. (2006). Cancer Cell Imaging and Photothermal Therapy in the Near-Infrared Region by Using Gold Nanorods. Journal of The American Chemical Society. 128 (6) DOI: /ja057254a
Ryu, J., et. al. (2014). Theranostic nanoparticles for future personalized medicine. Science Direct. (190)

19. Works Cited Digital images, retrieved from: