Healthcare (Commonwealth Union) — A research team from the National University of Singapore (NUS) has devised an innovative approach to improve the accuracy of cancer treatment by utilizing gold nanoparticles labeled with DNA barcodes.
Under the leadership of Assistant Professor Andy Tay from the Department of Biomedical Engineering at the College of Design and Engineering, as well as the Institute of Health Innovation & Technology at NUS, the study highlights how gold nanoparticles of specific geometries—such as triangular shapes—are particularly effective in transporting therapeutic nucleic acids and generating heat to destroy tumor cells through photothermal therapy. The research reveals that tumor cells exhibit distinct preferences for certain nanoparticle structures, paving the way for safer and more personalized cancer treatments.
The team’s groundbreaking method, published in Advanced Functional Materials on 24 November 2024, facilitates large-scale screening of nanoparticle shapes, sizes, and surface modifications, significantly reducing the cost of such analyses. Beyond cancer therapy, this technique holds promise for broader medical applications, including RNA-based treatments and targeted therapy for organ-specific diseases.
Gold isn’t just a symbol of luxury—it plays a crucial role in advanced cancer therapies. When reduced to nanoparticles about a thousand times smaller than a human hair, gold exhibits remarkable therapeutic properties. In photothermal therapy, for example, these tiny gold particles accumulate in tumors, where they absorb specific wavelengths of light and generate heat, effectively destroying cancer cells. Additionally, gold nanoparticles serve as precision drug carriers, delivering medication directly to targeted tumor sites for more effective treatment.
“But for these gold nanoparticles to work, they first need to get into the targeted sites successfully,” explained Assistant Professor Tay. “Think of it as a delivery person with a special key — if the key doesn’t fit the lock, the package won’t get through.”
Researchers of the study indicated that attaining this degree of accuracy requires identifying the ideal nanoparticle design—its form, dimensions, and surface characteristics must match the preferences of the target cells. However, current screening techniques for determining the most effective designs resemble the difficulty of finding a needle in a haystack. Additionally, these methods often fail to account for the varying preferences of different cell types within a tumor, including immune, endothelial, and cancer cells.
To overcome these obstacles, researchers at NUS adopted DNA barcoding. Each nanoparticle was labeled with a distinct DNA sequence, allowing the team to tag and track specific designs, similar to how parcels are registered in a postal system. Crucially, these barcodes enabled researchers to simultaneously monitor multiple nanoparticle variations in vivo, as their sequences could be easily retrieved and analyzed to determine the nanoparticles’ distribution within the body.
“We used thiol-functionalisation to securely anchor the DNA barcodes to the surface of the gold nanoparticles. This ensures the barcodes remain stable, resistant to enzymatic degradation and do not interfere with cellular uptake,” explained Assistant Professor Tay, emphasising a significant novelty of the researchers’ work.
The team’s research provides valuable insights into how nanoparticles interact within biological systems and highlights the importance of reconciling differences between laboratory (in vitro) and live-animal (in vivo) studies—differences that became evident with the round gold nanoparticles. These findings could help pave the way for developing nanoparticles that change shape or incorporate hybrid designs to enhance different phases of drug delivery.
Moreover, the study underscores the largely unexplored potential of nanoparticle shapes beyond spheres, which currently dominate U.S. Food and Drug Administration-approved designs. The DNA barcoding technique developed by the researchers could also be applied to screening other inorganic nanoparticles, such as those made of iron or silica, expanding possibilities for targeted drug delivery and precision medicine.
Moving forward, the team is growing its nanoparticle collection to 30 distinct designs to identify candidates capable of precisely targeting subcellular organelles. Promising designs will then be evaluated for their effectiveness in gene silencing and photothermal therapy for breast cancer. Assistant Professor Tay also noted that these discoveries could deepen the understanding of RNA biology and advance RNA-based drug delivery methods, which are becoming increasingly important in treating a wide range of diseases.
