Gold nanoparticles for cancer diagnosis and treatment

Rolf Loch
Although there are many techniques for cancer diagnosis and treatment, there is still a need for techniques that are more accurate and/or less invasive to the body. One promising scheme, which is useful for diagnosis as well as therapy, is to attach gold nanoparticles to tumor cells and illuminate them with infrared laser light. This technique is much less invasive than chemotherapy, X-ray therapy or surgery. Magnetic resonance imaging is noninvasive and capable of detecting cancer tumors when they are very small, but the equipment and its operation are very expensive, meaning that it is often used at a later stage, when the cancer is already more advanced. Ultrasound therapy offers a much cheaper alternative, but the high intensity sound waves that are necessary for treatment cause tissue heating and cavitation (creation of small pockets of gas in the bodily fluids or tissues that expand and contract/collapse). The long term influence of these side effects are still not known.

Because of their extremely small size, nanoparticles restrict the motion of electrons in one or more directions. This restriction, called quantum confinement, allows the properties of the particles to be modified by changing their size, in contrast to bulk material whose properties are independent of size. In particular, the properties of the surface become dominant and, in the case of noble metals, resonant electromagnetic radiation will induce large surface electric fields that enhance their radiative properties. This means that the particles absorb much more light than would normally be expected and the light that is not absorbed is scattered much more strongly than expected. This absorption and scattering is typically orders of magnitude stronger than the most strongly absorbing molecules and organic dyes. It has been found that gold nanorods and nanocages exhibit strong infrared (IR) absorption and biological compatibility, making them good candidates for use in biological systems. Huang et al. grew gold nanorods of different sizes and showed that different aspect ratios between the rod diameter and the length resulted in different absorption spectra. This showed that it is possible to produce biologically compatible nanoparticles with different optical properties. For further investigation, they chose nanoparticles with an aspect ratio of 3.9 because the absorption band overlaps the wavelength at 800 nm, which is the wavelength of a commercial Ti:sapphire laser. Furthermore, this wavelength is in a region where the light extinction of the human tissue is a minimum, resulting in a penetration depth up to 10 cm, which means that almost the whole human body is accessible.

Due to their strong scattering, gold nanorods have excellent potential as optical contrast agents for molecular imaging. Furthermore, the strongly absorbed IR radiation can be converted into heat efficiently, making it a promising potential photothermal therapeutic agent. In photothermal therapy, optical radiation is absorbed and transformed into heat. The heat causes the proteins and DNA to denature, irreversibly damaging the cell and, consequently, causing its death. Usually, photothermal therapy is done with visible light, which is absorbed by the agent as well as the tissue. The use of IR radiation is favourable because cell tissue is transparent to IR light, making it possible to diagnose and treat tumor cells deeper in the body. The convenient characteristic bioconjugation (binding to biomolecules) of gold nanostructures improves the target selectivity, so that they can stick to particular proteins, which makes it possible to target cancer cells with the nanoparticles and ensure that unhealthy cells receive most of the energy during therapy. As a result, the photothermal destruction of surrounding healthy tissue is minimized and the damage is much less than that caused during x-ray therapy.

Many cancer cells have copies of a protein, called Epidermal Growth Factor Receptor (EGFR), at their surface, which normal healthy tissue cells either do not have or have much fewer copies than cancer cells. The anti-EGFR antibody will naturally attach itself to this protein, which means that nanorods with anti-EGFR on their surface will end up attached to the surfaces of cancer cells. In the article from Huang et al., a synthetic method has been described to attach the gold nanorods to anti-EGFR antibodies. The process begins by coating the nanorods in a bilayer of cetyltrimethyl-ammonium bromide (CTAB). This is then exposed to polystyrenesulfonate (PSS) before the prepared nanorods are mixed with an antibody solution. The antibodies are probably bound to the PSS-coated nanorods by a mechanism called electrostatic physisorption or physical adsorption. This means that liquid molecules only adhere to the surface of a solid through a weak intermolecular interaction, called the Van der Waals force.

Consecutively, Huang et al. cultured (grow under controlled conditions) nonmalignant and malignant cells and immersed them into the anti-EGFR-conjugated nanorods solution for 30 minutes. They showed, by using surface plasmon resonant absorption spectroscopy (a standard technique to measure adsorption on surfaces of nanoparticles) and light scattering imaging, that the malignant cells are easily distinguished from the noncancerous cells due to the larger amount of EGFR on the malignant cells and consequent high concentration of nanorods.

By irradiating the samples with a continuous wave Ti:sapphire laser at different power densities, and successively staining them with a blue dye that only dead cells accumulate, it was shown that the intensity required to cause the destruction of malignant cells (10 W/cm²) is half the value necessary to cause death of normal healthy cells (20 W/cm²). Thus, the researchers have demonstrated the potential for gold nanorods to improve the efficacy of photothermal therapy. In another study by Chen et al., it was found that gold nanocages further lower the intensity threshold required to destroy cancerous cells to 1.5 W/cm².

In conclusion, the combination of nanotechnology and lasers, in the form of IR irradiated bioconjugated gold nanoparticles, can potentially be of use to effectively and safely diagnose and treat cancer, even in deeper parts of the human body. Primary fluorescent tests with mice were successfully performed by H. Wang et al. by injecting nanorods and imaging them as they flowed through blood vessels before these nanoparticles were, presumably, filtered out of the blood by the kidneys. Thus, we can expect that this promising, minimally invasive and cheap technique has shown great success in early trials. It has the potential to diagnose and treat any type of cancer, and, if proved safe, will become available for routine use in hospitals in the near future.