Gold nanoparticles have a wealth of pharmaceutical and medical uses. Notably, the ability of these nanoparticles to absorb light and turn this light into heat has put them at the center of ongoing cancer studies exploring their efficacy in destroying malignant cells. They have even been used as contrast agents in electron microscopy, but their ability to deliver other materials has made them candidates for drug and gene delivery and interesting to explore for inclusion in skin care.
Before you rush off to include gold nanoparticles in your new skin cream; however, brush up on the latest research by Tatsiana Mironava, PhD,* from Stony Brook University, who found that size, concentration and duration of application plays an important part in the toxicity of the material, with the wrong choice leading to a disruption of cell movement, cell replication and collagen contraction. In addition, at the wrong concentration, the gold nanoparticles inhibited the ability of pre-adipocytes to differentiate into mature adipocytes (adipogenesis).
Mironava’s decision to investigate gold nanoparticles was based on their potential in multiple industries. “Nanoparticles are promising because they have unique properties, but it is not clear if gold nanoparticles are completely safe,” she noted. “On the microscale, gold is inert, completely safe and approved for internal medicine, but on the nanoscale, the properties of gold are different.” Many scientists use them, assuming they are safe by analogy because their microscale counterparts are inert, but Mironava notes that scientists must be cognizant of the limitations and toxicity of different size gold nanoparticles.
Mironava’s team tested both 13 nm and 45 nm citrate-coated gold nanoparticles in cultures of adipose-derived stromal cells (pre-adipocytes). The sizes used, according to Mironava, were chosen for their obviously different toxicity levels. “Previous studies indicated that the level of toxicity was very different for these two sizes,” added Mironava, who sought to discover what happened to cells when exposed to toxic levels of gold nanoparticles.
The nanoparticles in a colloidal solution at various concentrations up to 15% v/v were cultured with the pre-adipocytes for allotted amounts of time. “We didn’t want to use more than 15% of the culture medium because we didn’t want to introduce too many variables at one time,” added Mironava. The cellular response was then checked at different time intervals, viewing the effect on protein synthesis and other cell properties such as migration and collagen contraction. It was compared to untreated pre-adipocytes as a control.
Toxicity of Nano Gold
Mironava noted that the larger nanoparticles, in this case 45 nm, are more toxic than the smaller nanoparticles (13 nm). Therefore, the team used lower concentrations of the colloidal gold solution for the bigger nanoparticles and higher concentrations (seven fold) of the colloidal gold solution for the smaller nanoparticles.
After culturing the pre-adipocytes with the colloidal gold solutions, Mironava noticed many changes to the cellular activity. “The level of different proteins was decreasing. We also found that the migration of the cells and the ability of the cells to contract collagen is suppressed,” noted Mironava. Specifically, the deposition of two main proteins of the extra-cellular matrix (ECM), collagen and fibronectin, is altered. “There is a larger suppression of collagen than the fibronectin, which results in the softening of the ECM.” The consequence of this softening is difficult to determine, according to Mironava, who found that, when cultured with dermal fibroblasts, the gold nanoparticles harden the ECM. “It is difficult to explain the consequence of [the opposite effects] because the change in these two proteins are required to differentiate pre-adipocytes to adipocytes.”
It is clear, however, that the decreased cell migration and decreased ability to contract collagen impact skin healing. “If your skin is wounded, collagen fibers in pre-adipocytes must contract or pull the wound closed. Therefore, wound healing is suppressed with toxic levels of the gold nanoparticles.”
Mironava also added that the gold nanoparticles suppress one of the main functions of pre-adipocytes, fat accumulation. “These cells differentiate themselves into adipocytes by accumulating lipids, but there was less lipid accumulation with the gold nanoparticles,” said Mironava. This inhibition of the differentiation of pre-adipocytes into adipocytes could be attributed to the ability of gold nanoparticles to increase the DLK1 protein, which has been found to inhibit adipogenisis. Mironava noted that this study is not complete, so the researchers do not know the whole story of the adipogenesis inhibition but plan to investigate further over the next five years.
Reversible Effect and Future
The important thing to note, according to Mironava, is that the effects of the gold nanoparticles are reversible at certain concentrations. “When we removed the nanoparticles from the cell culture, in a very short time, two weeks, the cells were able to recover from the concentration we gave them,” added Mironava. “It is important that if certain concentrations are not exceeded, the cells will be able to recover with no side effects.” The properties of the cells had returned to the same as the untreated cells.
The team plans to extend its study and further investigate its findings. “We want to see if these nanoparticles are able to suppress differentiation of other stem cells, which will be very important,” noted Mironava. The team also wants to look at the effect of inhibiting adipogenesis. “We want to see if there is a bigger picture; to find out if the suppression of the lipid accumulation, DLK1 protein, whatever else is involved, may actually cause local insulin dependence and diabetes.”
In addition to further investigating the above findings, the team plans to extrapolate the experiment in vivo. “Repeating the experiment with animals has to be done, but right now it is too early to say what is safe for creatures. In vivo studies will allow us to see if we can prevent fat deposition or fat accumulation.”