left: Tran Nguyen right: Overview of the electrochemical aptamer–based CytC monitor using microdissected tumor biopsies.
When researchers test drug treatments on tumor samples it can take two to three days to see the results of the treatment. Traditional testing approaches often rely on fluorescent markers or complex imaging techniques, which only provide a snapshot of tumor response at specific time points. This can slow the development of new drugs and understanding of the tumor. UW Bioengineering researchers led by Tran Nguyen, post-doctoral fellow with the Albert Folch lab, have developed a new platform that uses microdissected tumor biopsies. This platform retains the tumor’s native environment, including immune cells and vascular structures which allows for a more realistic representation of the tumor and localized drug testing in intact tissue samples.
The research team integrated aptamer-based electrochemical sensors into the platform, enabling them to detect specific biomarkers like cytochrome C (CytC), which is released during cell death in real-time. Aptamers are short, single-stranded DNA or RNA (ssDNA or ssRNA) molecules capable of selectively binding to specific targets, such as proteins, peptides, carbohydrates, small molecules, toxins and even living cells. The sensors used in the platform are placed in small wells and can monitor tissue samples taken from mice or humans. When the tumor tissue is treated with drugs, the sensors detect the release of cytochrome C, indicating the drug’s effect on killing cancer cells. This method is sensitive, capturing small but important changes in the tumor over time, which could be missed by other techniques.
These aptasensors are cost effective, function at both room temperature and incubator conditions, including the standard 37°C used for tissue growth, and provide dynamic measurements. Being able to monitor CytC levels continuously during drug-induced apoptosis (cell-death) gives researchers valuable insights into how tumors respond to treatments over time.
“This research could enhance the accuracy of preclinical drug testing, ultimately leading to more reliable predictions of drug efficacy in human patients and improving the efficiency of the clinical development process,” said Nguyen. “This platform also enables broader applications, such as its use in organ-on-chip systems, enhancing our ability to study various disease models under controlled conditions. The insights gained from this approach could lead to more effective cancer treatment strategies, particularly in tailoring therapies to individual patient profiles.”
Nguyen, who received her Ph.D. in biomedical engineering from the Weldon School of Biomedical Engineering, Purdue University, is the lead author of the study published in Science Advances. She collaborated with co-author Netzahualcóyotl Arroyo-Currás with Johns Hopkins School of Medicine and other researchers with UW Bioengineering, UW Surgery and Fred Hutch.