According to a study published in Advanced Functional Materials on November 24th, 2024, a group of researchers led by Assistant Professor Andy Tay from the Department of Biomedical Engineering in the College of Design and Engineering and Institute of Health Innovation & Technology at NUS has created a novel way to improve the accuracy of cancer treatment using gold nanoparticles tagged with DNA barcodes.
Asst Prof Andy Tay (right) and Ms Huang Xingyue (left) from NUS have developed a novel technique that tracks and optimizes gold nanoparticles for precise drug delivery to tumors. Image Credit: National University of Singapore
The study shows how specific-shaped gold nanoparticles, like triangles, are excellent at heating tumor cells during photothermal therapy and delivering therapeutic nucleic acids. These results reveal tumor cells' unique preferences for specific nanoparticle shapes, which could assist in creating safer and more efficient customized cancer treatments.
The team’s innovative method lowers associated screening expenses by enabling high-throughput screening of nanoparticle sizes, shapes, and alterations. The technique has wider therapeutic uses outside of cancer treatment, such as RNA delivery and organ-specific disease targeting.
Size and Shape Matter
Gold is more than just a bling. Gold nanoparticles shine as cancer treatment agents when reduced to a thousandth the breadth of human hair. For example, specks of precious metal are employed in photothermal therapy, in which particles given to the tumor site convert specific wavelengths of light to heat, killing cancer cells in the surrounding area. Gold nanoparticles can also act as messengers, delivering medications directly to specific locations within the tumor.
But for these gold nanoparticles to work, they first need to get into the targeted sites successfully. 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.
Andy Tay, Assistant Professor, Department of Biomedical Engineering, College of Design and Engineering and Institute of Health Innovation & Technology, National University of Singapore
Achieving this level of precision necessitates selecting the optimal nanoparticle design — its shape, size, and surface qualities must correspond to the preferences of target cells. However, conventional screening approaches for identifying optimal designs are like looking for a needle in a haystack. Furthermore, these methods frequently neglect the preferences of different cell types inside a tumor, ranging from immune to endothelial to cancer cells.
To address these issues, the NUS researchers used DNA barcoding. Each nanoparticle is labeled with a unique DNA sequence, allowing researchers to tag and track individual designs.
Importantly, these barcodes allowed the scientists to track various nanoparticle designs in vivo simultaneously because their sequences were simply recovered and examined to determine where the nanoparticles were located within the body.
Tay added, “We used thiol-functionalization 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.”
To demonstrate this, the researchers created nanoparticles of six distinct shapes and sizes and tracked their distribution and uptake across multiple cell types. They discovered that, despite low absorption in cell culture tests, round nanoparticles were good at targeting tumors in preclinical models because they were less likely to be removed by the immune system. In contrast, triangular nanoparticles performed well in both in vitro and in vivo testing, resulting in significant cellular uptake and robust photothermal characteristics.
Making Cancer Treatments Safer
The team's research sheds insight into nanoparticle interactions in biological systems and the necessity to bridge the gap between in vitro and in vivo discoveries, as demonstrated by the spherical gold nanoparticles. These findings could inform the development of shape-changing nanoparticles or intermediary designs that are tuned to optimize distinct stages of drug delivery.
Furthermore, the study demonstrates the untapped potential of studying nanoparticle shapes other than spheres, which dominate those approved by the US Food and Drug Administration. The DNA barcoding approach developed by the researchers might potentially be used to screen other inorganic nanoparticles such as iron and silica in vivo, expanding the possibilities for drug delivery and precision medicine.
Looking ahead, the researchers plan to expand their nanoparticle library to include 30 designs to uncover candidates capable of targeting subcellular organelles. Suitable candidates will subsequently be evaluated for their efficacy in gene silencing and photothermal therapy for breast cancer.
Assistant Professor Tay also stated that the discoveries could considerably increase the comprehension of RNA biology and advance RNA delivery techniques, which are increasingly being used in treatments to treat a variety of diseases.
“We have addressed a key challenge in cancer treatment — delivering drugs specifically to cancer tissues with greater efficiency. The Achilles’ heel of existing nanoparticle-based drugs is their assumption of uniform delivery across all organs, but the reality is that different organs respond differently. Designing optimally-shaped nanoparticles for organ-specific targeting enhances the safety and efficacy of nanotherapeutics for cancer treatment — and beyond,” Tay concluded.
Journal Reference:
Huang, X., et. al. (2024) In Vivo Screening of Barcoded Gold Nanoparticles Elucidates the Influence of Shapes for Tumor Targeting. Advanced Functional Materials. doi.org/10.1002/adfm.202411566