A group of researchers has created an innovative approach to improve cancer treatment precision by utilizing gold nanoparticles with DNA barcodes.
A group of researchers from the National University of Singapore (NUS) has created an innovative approach to improve cancer treatment precision by utilizing gold nanoparticles with DNA barcodes.
Under the guidance of Assistant Professor Andy Tay from the Department of Biomedical Engineering within the College of Design and Engineering and Institute of Health Innovation & Technology at NUS, this study reveals that gold nanoparticles, especially those shaped like triangles, are particularly effective in delivering therapeutic nucleic acids and heating cancer cells during photothermal therapy. These results highlight how certain shapes are preferentially absorbed by tumor cells, paving the way for tailored cancer treatments that are more effective and safer.
The team’s groundbreaking technique, elaborated in a publication in Advanced Functional Materials on November 24, 2024, allows for high-speed screening of various nanoparticle shapes, sizes, and modifications, leading to reduced costs in the screening process. This method not only has implications for cancer therapy but can also be applied in broader therapeutic contexts, including RNA delivery and targeting specific diseases in particular organs.
The Importance of Size and Shape
Gold transcends its ornamental value. When scaled down to about one-thousandth of a human hair’s width, gold nanoparticles emerge as key players in cancer treatment. These tiny particles are utilized in photothermal therapy, where they absorb specific light wavelengths and convert them into heat, destroying nearby cancer cells. Moreover, gold nanoparticles can act as carriers, channeling medications straight to specific tumor areas.
“For gold nanoparticles to function effectively, they must first reach their intended sites,” stated Asst Prof Tay. “Imagine it like a delivery person with a special key—without the right key, the package cannot pass through the lock.”
Achieving this level of targeting necessitates pinpointing the ideal nanoparticle design—its shape, dimensions, and surface traits must resonate with the preferences of the target cells. However, current screening approaches to discover the best designs resemble searching for a needle in a haystack, often missing the unique preferences of various cell types within a tumor, including immune, endothelial, and cancer cells.
To address these hurdles, the NUS team employed DNA barcoding. Each nanoparticle carries a distinct DNA sequence, allowing the researchers to tag and monitor individual designs, similar to how packages are registered in a shipping system. This technology enabled tracking of multiple nanoparticle designs concurrently in living organisms, as the sequences could be easily extracted and analyzed to determine the nanoparticles’ positions within the body.
“We utilized thiol-functionalization to firmly attach the DNA barcodes to the surface of the gold nanoparticles. This ensures that the barcodes remain stable, resistant to breakdown by enzymes, and do not interfere with how cells absorb them,” explained Asst Prof Tay, emphasizing a crucial aspect of their approach.
To validate their findings, the researchers created nanoparticles in six distinct shapes and sizes, observing their distribution and absorption across various cell types. They discovered that while round nanoparticles showed poor absorption in laboratory settings, they were highly effective in targeting tumors in preclinical models, as they were less prone to elimination by the immune system. Conversely, triangular nanoparticles performed brilliantly in both laboratory and live tests, demonstrating high cellular absorption and strong heating capabilities.
Enhancing the Safety of Cancer Treatments
The team’s research highlights the interactions between nanoparticles and biological systems, underlining the necessity to reconcile differences between in vitro and in vivo results, as illustrated by the findings on round gold nanoparticles. These insights could inform the development of adaptable nanoparticles or intermediate designs that optimize various phases of drug delivery.
The study also sheds light on the unexplored possibilities of nanoparticle shapes other than spheres, which are predominantly represented in those authorized by the U.S. Food and Drug Administration. The DNA barcoding technique could also be utilized to analyze other inorganic nanoparticles, such as iron and silica, in vivo, thereby expanding opportunities for drug delivery and precision medicine.
Looking to the future, the researchers are broadening their nanoparticle library to include 30 designs to identify candidates capable of targeting specific subcellular organelles. The successful candidates will then undergo testing for their effectiveness in gene silencing and photothermal therapy for breast cancer. Asst Prof Tay also mentioned that these discoveries could greatly enhance our understanding of RNA biology and refine RNA delivery methods, which are increasingly relevant in therapies for various illnesses.
“We have tackled a significant challenge in cancer treatment—ensuring drugs reach cancer tissues more precisely,” stated Asst Prof Tay. “Current nanoparticle-based drugs often assume uniform delivery across organs, but the reality is that different organs react differently. By designing nanoparticles specifically shaped for targeted organ delivery, we can improve the safety and efficacy of nanomedicine for cancer care and beyond.”
