Golden pop: nanoparticles for SERS

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  • Published: Feb 1, 2011
  • Author: David Bradley
  • Channels: Raman
thumbnail image: Golden pop: nanoparticles for SERS

Kernel of the problem

Gold nanoparticles that resemble tiny popcorn kernels can be produced using a simple two-step process. Researchers at Jackson State University in the US have used these particles in SERS (surface-enhanced Raman spectroscopy) experiments to detect malignant prostate cancer at just the 50-cell level. The same particles can also be activated to kill the cells.

Chemists Wentong Lu, Anant Kumar Singh, Sadia Afrin Khan, Dulal Senapati, Hongtao Yu, and Paresh Chandra Ray of Jackson State University, in Jackson, Mississippi, USA, explain that prostate cancer is the second leading cause of cancer-related death among the American male population; the cost of treating prostate cancer patients is about $10 billion each year in the US alone. They add that current treatments are usually ineffective against the disease once it is in the advanced stages and they also have severe side effects. A highly sensitive diagnostic that incorporated technology to kill any malignant cells detected could lead to much improved results for patients. "New approaches to treat prostate cancer that do not rely on traditional therapeutic regimes are urgently needed for public health as well as the world economy," the team says.

The team explains that various types of gold nanoparticle with tuneable near-infrared optical properties have been investigated and exploited in the thermal destruction of cancer cells and could lead, assuming successful clinical trial results to a new approach to treatment known as "photothermal nanotherapy". Before that can happen finding a way to monitor the effects and to ensure the right cells are being targeted is needed, which is where Raman nanopopcorn comes in. The team has now synthesised gold nanoparticles that might fulfil this role.

"In nano-popcorn, the central sphere acts as an electron reservoir, while the tips are capable of focusing the field at their apexes, which will provide a sufficient field of enhancement," they explain. "As a result, in popcorn-shaped gold nanoparticles, low cross-section Raman signals can be amplified by several orders of magnitude, particularly in narrow, nanoscale corners and edges."

Targeted prostate cells

The researchers add that their experimental data show that with LNCaP human prostate cancer cells the nanopopcorn behave as multifunctional entities. The nanoparticles generate several hotspots as well as enhancing significantly the Raman signal by several orders of magnitude. The result is that the nanopopcorn allows detection of prostate cancer even when a mere 50 cells are present in a sample. Once bound to prostate cancer cells, the gold nanoparticles can absorb light and convert it to heat, raising the local temperature to 48 Celsius, which is sufficient to kill the tumour cells to which they are attached.

"Our in situ time-dependent results demonstrate for the first time that, by monitoring SERS intensity changes, one can monitor photothermal nanotherapy response during the therapy process," the team adds. This could have enormous potential in combined rapid sensing and treatment.

As synthesized, the free nanoparticles would be highly toxic to all cells in the body, so the team attaches tumour-targeting aptamers and monoclonal antibodies to the nanopopcorn to allow them to latch on to prostate cancer cells hopefully without interfering with healthy cells.

During this experiment, the investigators noted that the SERS signal intensity decreased as the tumour cells died. Further study showed that there was a direct, linear correlation between the number of cells killed and the reduction in signal intensity, suggesting that this type of measurement could prove useful in assessing the therapeutic effect following photothermal therapy.

PSMA circumvention

The work has also circumvented a problem associated with identification of cancer cells at the early stages. LNCaP is a well-characterized human prostate cancer cell line, which expresses prostate-specific membrane antigen; levels of PSMA expressed rise as the cancer progresses. However, there is recent evidence that other, normal, tissues, including duodenal epithelium, kidney, endometrium and breast, also express PSMA. This may mean that specifically targeting prostate cancer in studies, investigation and therapy may have been distorted by the presence of PSMA in other healthy tissues. The new work exploits the gold nanopopcorn using conjugated PSMA-specific targets: anti-PSMA antibody and Raman dye (Rh6G) attached to A9 RNA anti-PSMA aptamers, which are not only specific to PSMA but are target cell specific based on additional biochemical characteristics.

 


The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

Credit: American Chemical Society/JACS Gold nanoparticles that resemble tiny popcorn kernels can be produced using a simple two-step process. Researchers at Jackson State University in the US have used these particles in SERS (surface-enhanced Raman spectroscopy) experiments to detect malignant prostate cancer at just the 50-cell level. The same particles can also be activated to kill the cells.
Nano popcorn vs. prostate cancer

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