The role of microRNAs in the detection of various types of cancer has become increasingly evident over the past several years. However, a major drawback of using these molecules as a diagnostic indicator of disease has been developing a method that is sensitive enough to detect minuscule amounts of the genetic material in a timeframe that is relevant to therapeutic intervention.
Now a group of researchers from the Indiana University-Purdue University Indianapolis schools of science and medicine and the Indiana University Melvin and Bren Simon Cancer Center have created a simple, ultrasensitive microRNA sensor that holds promise for the design of new diagnostic strategies and, potentially, for the prognosis and treatment of pancreatic and other cancers.
“We used the fundamental concepts of nanotechnology to design the sensor to detect and quantify biomolecules at very low concentrations,” explained co-senior author and sensor developer Rajesh Sardar, Ph.D., assistant professor of chemistry at IUPUI. “We have designed an ultrasensitive technique so that we can see minute changes in microRNA concentrations in a patient's blood and confirm the presence of pancreatic cancer.”
The findings from this study were published recently in ACS Nano through an article entitled “Label-Free Nanoplasmonic-Based Short Noncoding RNA Sensing at Attomolar Concentrations Allows for Quantitative and Highly Specific Assay of MicroRNA-10b in Biological Fluids and Circulating Exosomes.”
MicroRNAs are small non-coding stretches of RNA (about 22 nucleotides long) found in plants, animals, and some viruses that regulate the expression or silencing of mRNA molecules. In recent years, researchers have discovered that these regulatory molecules contain unique sequence signatures that play an important part in carcinogenesis and can be found circulating in the bloodstream of patients with various tumors, such as those with pancreatic cancer.
“If we can establish that there is cancer in the pancreas because the sensor detects high levels of microRNA-10b or one of the other microRNAs associated with that specific cancer, we may be able to treat it sooner,” noted co-senior author Murray Korc, M.D., professor of medicine and cancer research at the IU School of Medicine.
“That's especially significant for pancreatic cancer, because for many patients it is symptom-free for years or even a decade or more, by which time it has spread to other organs when surgical removal is no longer possible and therapeutic options are limited,” Dr. Korc remarked. “For example, diagnosis of pancreatic cancer at an early stage of the disease followed by surgical removal is associated with a 40 percent five-year survival. Diagnosis of metastatic pancreatic cancer, by contrast, is associated with a life expectancy that is often only a year or less.”
In the current study, the investigators assembled the nanoparticles using an ultrasensitive localized surface plasmon resonance-based microRNA sensor with single nucleotide specificity using gold nanoprisms attached to a solid substrate. The researchers used their new sensors to detect microRNA-10b from in vitro pancreatic cell lines, tissue culture media, and human plasma at attomolar (10-18 M) concentrations. They found that microRNA10b levels were significantly higher in patients with pancreatic cancer than patients with chronic pancreatitis or normal controls.
“The beauty of the sensor designed by Dr. Sardar is its ability to accurately detect mild increases in microRNA levels, which could allow for early cancer diagnosis,” Dr. Korc added. Moreover, studies have shown that microRNAs not only play important roles in cancer but in other diseases affecting global populations such as diabetes and cardiovascular disorders.
“Using gold nanoprisms may sound expensive, but it isn't because these particles are so very tiny,” Dr. Sardar stated. “It's a rather cheap technique because it uses nanotechnology and needs very little gold. $250 worth of gold makes 4,000 sensors. Four thousand sensors allow you to do at least 4,000 tests. The low cost makes this technique ideal for use anywhere, including in low-resource environments in this country and around the world.”