NUS researchers are developing DNA-barcoded nanoparticles for targeted cancer therapy

NUS researchers are developing DNA-barcoded nanoparticles for targeted cancer therapy

A team of researchers from the National University of Singapore (NUS) has developed a novel method to improve the precision of cancer treatment using gold nanoparticles labeled with DNA barcodes.

Led by Assistant Professor Andy Tay from the Department of Biomedical Engineering at the College of Design and Engineering and the Institute of Health Innovation & Technology at NUS, the study demonstrates heating tumor cells during photothermal therapy. These results revealed the different preferences of tumor cells for certain nanoparticle configurations, which could enable the development of personalized cancer treatments that are safer and more effective.

The team's novel technique, revealed in a paper published inAdvanced functional materialsOn November 24, 2024, enables high-throughput screening of nanoparticle shapes, sizes and changes, reducing associated screening costs. Beyond cancer treatment, the method has broader therapeutic applications, including RNA delivery and disease targeting at the organ-specific level.

Size and shape matter

Gold is more than just bling. When gold nanoparticles are reduced to about one-thousandth the width of a human hair, they shine as therapeutic agents for cancer therapy. For example, patches of the precious metal are used in photothermal therapy, in which particles delivered to the tumor site convert specific wavelengths of light into heat, killing surrounding cancer cells. Gold nanoparticles can also serve as drug messengers to deliver drugs directly to specific locations within a tumor.

However, for these golden nanoparticles to work, they must first successfully enter the target sites. 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. “

Assistant Professor Andy Tay, Department of Biomedical Engineering, College of Design and Engineering and Institute of Health Innovation and Technology at NUS

To achieve this level of precision, the right nanoparticle design must be found – its shape, size and surface properties must match the preferences of the target cells. However, existing screening methods for determining optimal designs are like looking for needles in a haystack. Furthermore, these methods often miss the preferences of different cell types within a tumor, from immune to endothelial to cancer cells.

To address these challenges, NUS researchers turned to DNA barcoding. Each nanoparticle is marked with a unique DNA sequence, which allowed the researchers to mark and track individual designs, similar to registering a package ready to be sent by mail in a delivery system. Importantly, these barcodes allowed the team to simultaneously monitor multiple nanoparticle designs in vivo because their sequences could be easily extracted and analyzed to pinpoint the nanoparticles' locations in the body.

"We used thiol functionalization to securely anchor the DNA barcodes to the surface of the gold nanoparticles. This ensures the team's work.

To demonstrate this, the researchers presented nanoparticles in six different shapes and sizes, where their distribution and uptake across different cell types were monitored. They found that despite poor uptake in cell culture studies, round nanoparticles were excellent for tumors in preclinical models because they were less likely to be cleared by the immune system. On the other hand, triangular nanoparticles have emerged from both in vitro and in vivo tests, resulting in high cellular uptake and strong photothermal properties.

Making cancer treatments safer

The team's work illuminates the interactions between nanoparticles in biological systems and the need to bridge the discrepancies between in vitro and in vivo findings, as evidenced by the round gold nanoparticles revealed by the round gold nanoparticles. These findings could guide the development of shape-morphing nanoparticles or intermediate designs tailored to optimize different stages of drug delivery.

Additionally, the research illuminates the untapped potential to explore nanoparticle shapes beyond the spheres that dominate those approved by the U.S. Food and Drug Administration. The researchers' DNA barcoding method could also extend to other inorganic nanoparticles such as iron and silica in vivo, expanding the scope for drug delivery and precision medicine.

Looking forward, the researchers are expanding their nanoparticle library by 30 designs to identify candidates that can target subcellular organelles. Suitable ones are then tested for their effectiveness in gene silencing and photothermal therapy for breast cancer. Asst Prof Tay also shared that the findings could significantly improve our understanding of RNA biology and the advancement of RNA delivery techniques, which are increasingly being applied in therapeutics to treat various diseases.

“We have addressed a key challenge in cancer treatment – ​​submitting drugs specifically for cancer tissues with greater efficiency,” said Asst Prof Tay. "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 improves the safety and effectiveness of cancer nanotherapeutics for cancer treatment - and beyond."

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