NUS researchers pioneer DNA-tagged gold nanoparticles for targeted cancer therapy. newswise

A team of NUS researchers has developed a novel method to increase the accuracy of cancer treatment using gold nanoparticles tagged with DNA barcodes.

Led by Assistant Professor Andy Tai Department of Biomedical Engineering In College of Design and Engineering And Institute of Health Innovation and Technology At NUS, the study demonstrates how gold nanoparticles of specific shapes, such as triangles, excel at delivering therapeutic nucleic acids and heating tumor cells during photothermal therapy. These findings highlight specific preferences of tumor cells for certain nanoparticle configurations, which may enable the development of personalized cancer treatments that are safer and more effective.

The team’s novel technique, detailed in a paper published in advanced functional materials 24 Nov 2024 Enables high-throughput screening of nanoparticle sizes, shapes, and modifications, thereby reducing associated screening costs. In addition to cancer treatment, this method has broad therapeutic applications, including RNA delivery and targeting of diseases at an organ-specific level.

size and shape matter

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

“But for these gold nanoparticles to work, they must first successfully enter target sites,” said Assistant Professor Tai. “Think of it as a delivery person with a special key – if the key doesn’t fit in the lock, the package won’t get delivered.”

Achieving this level of precision requires finding the right nanoparticle design – its size, shape and surface properties must match the preferences of target cells. However, existing screening methods to pinpoint the optimal design are akin to searching for needles in a haystack. Furthermore, these methods often ignore the preferences of different types of cells within the tumor, ranging from immune to endothelial to cancer cells.

To overcome these challenges, NUS researchers turned to DNA barcoding. Each nanoparticle is tagged with a unique DNA sequence, with which researchers can tag and track individual designs, like registering a parcel being sent by post in a delivery system. Importantly, these barcodes enabled the team to monitor multiple nanoparticle designs simultaneously in vivo, as their sequences could be easily extracted and analyzed to trace the whereabouts of the nanoparticles within the body. Could have done.

“We used thiol-functionalization to safely attach DNA barcodes to the surface of gold nanoparticles. This ensures that the barcodes remain stable, resistant to enzymatic degradation and do not interfere with cellular absorption,” said Assistant Professor Tai, highlighting an important novelty of the team’s work.

To demonstrate this, the researchers prepared nanoparticles in six different shapes and sizes, where their distribution and uptake into different types of cells was monitored. They found that the round nanoparticles, despite performing poorly in cell culture studies, were excellent at targeting tumors in preclinical models because they were less likely to be eliminated by the immune system. On the other hand, the triangular nanoparticles performed excellently in both in vitro and in vivo tests, resulting in high cellular uptake and strong photothermal properties.

making cancer treatment safer

The team’s work highlights the interactions of nanoparticles in biological systems and the need to bridge the discrepancies between in vitro and in vivo findings, as demonstrated by the round gold nanoparticles. These insights may guide the development of shape-transforming nanoparticle or intermediate designs designed to optimize different stages of drug delivery.

Additionally, the research also highlights the untapped potential of nanoparticle size exploration beyond the fields, which are dominated by those approved by the US Food and Drug Administration. The researchers’ DNA barcoding method can also be extended to screening other inorganic nanoparticles such as iron and silica in vivo, thereby expanding the scope of drug delivery and precision medicine.

Looking ahead, the researchers are expanding their nanoparticle library to include 30 designs to identify candidates capable of targeting subcellular organelles. Suitable ones will then be tested for their efficacy in gene silencing and photothermal therapy for breast cancer. Assistant Professor Tai also shared that the findings could significantly improve our understanding of RNA biology and advanced RNA delivery technologies, which are increasingly being applied in therapeutics for the treatment of various diseases.

“We have solved a major challenge in cancer treatment – ​​delivering drugs specifically to cancer tissue with greater efficiency,” said Assistant Professor Tai. “The Achilles heel of existing nanoparticle-based drugs is their assumption of uniform distribution in all organs, but the reality is that different organs respond differently. Designing optimally sized nanoparticles for organ-specific targeting increases the safety and efficacy of nanotherapeutics for cancer treatment and beyond.