NUS Scientists Develop DNA-Guided Gold Nanoparticles for Targeted Cancer Therapy “`

1f17b44939dbbb21ecdefb7c8766b20f NUS researchers pioneer DNA-tagged gold nanoparticles for targeted cancer treatment

A new method uses DNA barcoding to track and optimize gold nanoparticles for precise tumor drug delivery, leading to safer and more effective cancer treatments.

SINGAPORE, Jan. 24, 2025 — Researchers at the National University of Singapore (NUS) have created a new approach for improving the accuracy of cancer treatment using DNA-tagged gold nanoparticles.

National University of Singapore Logo (PRNewsFoto/National University of Singapore)

Led by Assistant Professor Andy Tay at NUS, the research shows how specific gold nanoparticle shapes, like triangles, are particularly effective at delivering therapeutic nucleic acids and heating tumor cells during photothermal therapy. These findings highlight that tumor cells prefer certain nanoparticle configurations, suggesting the potential for safer and more effective personalized cancer treatments.

This innovative technique, published in on 24 November 2024, allows for high-throughput screening of nanoparticle shapes, sizes, and modifications, lowering screening costs. Beyond cancer treatment, this method has broader therapeutic potential, including RNA delivery and organ-specific disease targeting.

Size and shape matter

At the nanoscale, gold acts as a therapeutic agent for cancer. It’s used in photothermal therapy, where nanoparticles at the tumor site convert light into heat, destroying cancer cells. Gold nanoparticles also deliver drugs directly to specific tumor areas.

“However, successful delivery of these nanoparticles to their target sites is crucial,” explained Asst Prof Tay. “It’s like a delivery person needing the right key; if it doesn’t fit, the package won’t be delivered.”

Achieving this precision requires finding the optimal nanoparticle design—its shape, size, and surface properties must match the target cells’ preferences. Current screening methods are inefficient and often overlook the varying preferences of different cell types within a tumor.

The NUS researchers used DNA barcoding to overcome these challenges. Each nanoparticle is tagged with a unique DNA sequence, allowing tracking of individual designs, much like parcel tracking. This enables simultaneous monitoring of multiple nanoparticle designs in vivo.

“We used thiol-functionalisation to firmly attach the DNA barcodes to the nanoparticles, ensuring barcode stability, resistance to degradation, and no interference with cellular uptake,” said Asst Prof Tay, emphasizing a key innovation.

Testing six different nanoparticle shapes and sizes, the researchers monitored their distribution and uptake across various cell types. Round nanoparticles, despite poor uptake in cell cultures, effectively targeted tumors in preclinical models due to reduced immune system elimination. Triangular nanoparticles excelled in both in vitro and in vivo tests, showing high cellular uptake and strong photothermal properties.

Making cancer treatments safer

This research highlights the importance of understanding nanoparticle interactions in biological systems and bridging the gap between in vitro and in vivo findings, as shown by the round gold nanoparticles. This understanding could lead to shape-morphing nanoparticles or designs optimized for different drug delivery stages.

The research also reveals the potential of exploring nanoparticle shapes beyond the spheres that dominate FDA-approved designs. The DNA barcoding method could be used to screen other inorganic nanoparticles, expanding applications in drug delivery and precision medicine.

The researchers plan to expand their nanoparticle library to 30 designs to find candidates targeting subcellular organelles. Suitable candidates will be tested for gene silencing and photothermal therapy in breast cancer. Asst Prof Tay also noted that the findings could significantly advance our understanding of RNA biology and RNA delivery techniques for various diseases.

“We’ve addressed a major challenge in cancer treatment—efficiently delivering drugs specifically to cancer tissues,” said Asst Prof Tay. “Existing nanoparticle-based drugs assume uniform delivery, but organs respond differently. Optimally-shaped nanoparticles for organ-specific targeting improve the safety and efficacy of nanotherapeutics for cancer and beyond.”

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SOURCE National University of Singapore

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