Searching for Gold (Nanoparticles)
By Amy Jia
The past few decades have seen an alarming rise in both the number of new cancer cases and the number of cancer-related deaths. In fact, the American Cancer Society projects a 50% increase in worldwide cases by the year 2030, with a corresponding 60% increase in the disease’s mortality rate within the same time frame.1 The need for a reliable, safe way to detect cancerous growths in their early stages has never been more imperative than now, and it was this pursuit that inspired my research with Dr. Jie Zheng at the University of Texas at Dallas. My objective was to find nanoparticles that localize within tumors and exhibit low toxicity, high renal clearance (i.e. the ability to be removed from the body through urine), and strong fluorescence.
Nanoparticles are microscopic particles of matter, with at least one of their dimensions in the range of 1 to 100 nanometers (1 nanometer = 1 * 10-9 meters).2 Because nanoparticles are able to circulate widely throughout the body, as well as enter and bind to specific cells, they are often used in modern therapeutics as drug delivery vehicles or image enhancers for diseased tissues.2 My research involved the use of amino acid coated gold nanoparticles, which are synthesized by combining gold acid (Au) and amino acid (AA) solutions. These nanoparticles are fluorescent under ultraviolet light and are designed to highlight tumor sites, as shown in the series of images below:
Fig. 1: Representative in vivo NIR fluorescence images of tumor-bearing mice with fluorescent gold nanoparticles. (Note: Arrow indicates tumor.)3
The ability to “tune” the fluorescence of these nanoparticles—much like one would tune a radio—to optimize the viewing of such growths would be immensely beneficial and allow for a new form of tumor imaging.
My research aimed to determine the specific combination and concentration of amino acids that would produce the optimal fluorescence. This would enable doctors to image and treat tumors in their early stages with minimal toxic effects on the body. Twenty amino acids—including glycine, cysteine, histidine, and methionine—were surfaced onto gold nanoparticles in 1:1, 1:2, and 2:1 Au:AA ratios, with the fluorescence monitored over a seven-day period. After testing each sample and analyzing their individual emission spectrums (i.e. the wavelength(s) at which the solution was most strongly fluorescent), the cysteine and histidine nanoparticle solutions were found to have the greatest difference in emission. As a result, I chose to focus on these two amino acids.
In particular, I was interested in whether combining cysteine and histidine would produce a noticeable shift in fluorescence. As a result, cysteine and histidine were further tested using the same ratios of gold acid to amino acid solutions (1:1, 1:2, and 2:1 Au:AA ratios for cysteine, histidine, and a cysteine-histidine combination), and monitored over a seven-day period. After seven days, the emission wavelength of the histidine nanoparticles was found at 450 nm (violet/blue light); the emission wavelength of the cysteine nanoparticles was found at 475/650 nm (blue/cyan light and red light); and the emission wavelength of the cysteine-histidine nanoparticles was found at 500 nm (green light). This range of wavelengths emitted by different cysteine-histidine nanoparticles comes in handy during nanoparticle-assisted tumor imaging, which requires that the nanoparticles emit a different wavelength of light than the tumor they are meant to track. Because different tissues in the human body emit different wavelengths of this natural background fluorescence, also known as autofluorescence, the wide range of wavelengths emitted by different cysteine-histidine nanoparticles allows scientists to distinguish between a wide variety of tissues during imaging.
The results of my experiment addressed my initial objective of tuning fluorescence using nanoparticles of different amino acid combinations: the combination of cysteine and histidine nanoparticles produced a noticeable shift in emission compared to the two types of nanoparticles tested separately. Tunable fluorescence has significant implications for the future of imaging technology, as doctors may be able to use it to highlight specific sites of cancerous growths and adjust for the body’s autofluorescence. While there is still much work to do in perfecting cancer diagnosis, the ability to manipulate the emission spectrums of gold nanoparticles to identify malignant tumors early on will certainly take the scientific world one step closer to success.
- “Cancer Statistics.” National Cancer Institute, 22 March 2017, https://www.cancer.gov/about-cancer/understanding/statistics.
- Dobson, Peter, Stephen King, and Helen Jarvie. “Nanoparticle.” Encyclopædia Britannica, 21 April 2016, https://www.britannica.com/science/nanoparticle.
- “Zheng’s Group.” Zheng’s Lab @ UT Dallas, https://www.utdallas.edu/~jiezheng/. Accessed 24 July 2017.