Using DNA barcoding, the novel technique tracks and
optimises gold nanoparticles for precise drug delivery to tumours,
advancing cancer therapies that are safer and more
effective
SINGAPORE, Jan. 24,
2025 /PRNewswire/ -- A team of researchers from the
National University of Singapore (NUS)
has developed a novel method to enhance the precision of cancer
treatment using gold nanoparticles tagged with DNA barcodes.
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, the study demonstrates how
gold nanoparticles of specific shapes, such as triangles, excel in
delivering therapeutic nucleic acids and heating tumour cells
during photothermal therapy. These findings uncover the distinct
preferences of tumour cells for certain nanoparticle
configurations, which could enable the development of personalised
cancer treatments that are safer and more effective.
The team's novel technique, detailed in a paper published in
Advanced Functional Materials on 24 November 2024, enables high-throughput
screening of nanoparticle shapes, sizes and modifications, reducing
associated screening costs. Beyond cancer treatment, the method has
broader therapeutic applications, including RNA delivery and
targeting diseases at the organ-specific level.
Size and shape matter
Gold is more than just bling. When reduced to about
one-thousandth the width of human hair, gold nanoparticles shine as
therapeutic agents for cancer therapy. For instance, specks of the
precious metal are used in photothermal therapy, where particles
delivered to the tumour site convert specific wavelengths of light
to heat, killing surrounding cancer cells. Gold nanoparticles can
also serve as messengers to deliver drugs directly to specific
locations within a tumour.
"But for these gold nanoparticles to work, they first need to
get into the targeted sites successfully," said Asst Prof Tay.
"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."
Achieving this level of precision requires finding the right
nanoparticle design — its shape, size and surface properties must
align with the preferences of target cells. However, existing
screening methods to pinpoint optimal designs are akin to searching
for needles in a haystack. Moreover, these methods often overlook
the preferences of different cell types within a tumour, from
immune to endothelial to cancer cells.
To tackle these challenges, the NUS researchers turned to DNA
barcoding. Each nanoparticle is tagged with a unique DNA sequence,
with which the researchers could tag and track individual designs,
much like registering a parcel to be shipped 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 analysed to locate the
nanoparticles' whereabouts within the body.
"We used thiol-functionalisation 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," said Asst Prof Tay,
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
across various cell types were monitored. They found that round
nanoparticles, despite showing poor uptake in cell culture studies,
were excellent in targeting tumours in preclinical models as they
were less likely to be eliminated by the immune system. On the
other hand, triangular nanoparticles excelled in both in vitro and
in vivo tests, resulting in high cellular uptake and strong
photothermal properties.
Making cancer treatments safer
The team's work shines a light on nanoparticle interactions in
biological systems and the need to bridge discrepancies between in
vitro and in vivo findings, as evidenced by those revealed by the
round gold nanoparticles. These insights could guide the
development of shape-morphing nanoparticles or intermediate designs
tailored to optimise different stages of drug delivery.
Additionally, the research also illuminates the untapped
potential of exploring nanoparticle shapes beyond spheres, which
dominate those approved by the U.S. Food and Drug Administration.
The researchers' DNA barcoding method could also extend to screen
other inorganic nanoparticles such as iron and silica in vivo,
broadening the scope for 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. Asst Prof Tay also shared that the findings could
significantly improve our understanding of RNA biology and advance
RNA delivery techniques, which are increasingly being applied in
therapeutics for treatment of various diseases.
"We have addressed a key challenge in cancer treatment —
delivering drugs specifically to 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 enhances the safety and efficacy of
nanotherapeutics for cancer treatment — and beyond."
Read more at:
https://news.nus.edu.sg/dna-tagged-gold-nanoparticles-for-targeted-cancer-treatment/
View original content to download
multimedia:https://www.prnewswire.com/news-releases/nus-researchers-pioneer-dna-tagged-gold-nanoparticles-for-targeted-cancer-treatment-302359513.html
SOURCE National University of
Singapore