Nanotechnology (Commonwealth Union) – The mitochondria is an essential component of the cell which plays a key role as the energy supplier. It plays a vital role in the overall metabolism.
A new screening platform has demonstrated the ability to pinpoint nanoparticles that target tumour mitochondria for precision cancer therapy. Scientists at the National University of Singapore (NUS) have developed a high-throughput system that rapidly evaluates dozens of nanoparticle designs in living models to identify those that can deliver therapies directly to mitochondria, the energy hubs of cancer cells.
The team tagged gold nanoparticles with unique DNA “barcodes,” allowing them to track and compare multiple designs simultaneously within tumours. It rapidly identified the most effective formulations for targeting the mitochondria, an important subcellular compartment for cancer therapy.
The platform also allows systematic exploration of the impact of factors such as particle shape, size and surface chemistry on tumour accumulation and mitochondrial delivery. Two of the nanoparticles tested showed promise. Interestingly, in preclinical trials, the folic acid-modified cubic gold nanoparticle combined with mitochondria-targeting RNA therapy and mild photothermal treatment achieved 99% tumour regression.
Led by Assistant Professor Andy Tay of NUS’s Department of Biomedical Engineering and the Institute for Health Innovation & Technology, the research demonstrates how extensive libraries of nanomaterials can be efficiently screened in living systems. The findings offer a rational framework for designing nanoparticles that deliver treatments with unprecedented precision. The study was published in Advanced Materials on 17 February 2026.
Mitochondria are promising targets for cancer treatments because they control crucial functions like energy generation and programmed cell death. Directly delivering drugs to these organelles can interfere with tumour metabolism and induce cancer cell death. Yet, nanoparticles face multiple biological hurdles before reaching mitochondria: they must navigate the bloodstream, infiltrate tumours, enter cells, and evade cellular compartments that would otherwise degrade their therapeutic payload.
Professor Thomas Seyfried a leading cancer researcher has presented extensive research demonstrating the key role of the mitochondrial dysfunction in cancer and how the mitochondria should be a key focus in cancer treatment.
Assistant Professor Tay indicated that guiding nanoparticles to the right location inside the body is like sending them through a complex obstacle course.
He pointed out that the utilization of DNA barcodes lets them monitor many nanoparticle designs simultaneously in living systems and rapidly determine which ones successfully overcome these biological challenges.
In the research, each gold nanoparticle variant was labeled with a distinct DNA sequence, enabling the team to track its distribution via next-generation sequencing. They examined a library of 30 nanoparticles that differed in size, shape, and targeting molecules. After administering the pooled nanoparticles to tumour-bearing preclinical models, the researchers assessed where each formulation accumulated — from entire organs to specific tumour cells and ultimately to mitochondria.
This multiplexed strategy produced over 1,000 in vivo data points while requiring roughly 30 times fewer animal models than traditional one-by-one testing methods.
This research expands on the team’s earlier study from November 2024, which initially showcased how DNA barcoding can be used to monitor nanoparticle distribution in tumours. Whereas the prior work examined six nanoparticle designs at the tissue level, the new study significantly broadens the nanoparticle library and adapts the platform to investigate their behavior at both cellular and subcellular levels.
“The results revealed an important insight: nanoparticles that accumulated efficiently in tumours were also far more likely to reach mitochondria,” explained Assistant Professor Tay. “In other words, successful tumour targeting appears to be a prerequisite for effective subcellular delivery.”
Out of the nanoparticle formulations evaluated, two stood out to the researchers. Large spherical particles coated with folic acid showed high tumour accumulation, partly because a protective protein layer extended their circulation time in the bloodstream. In contrast, large cubic nanoparticles were taken up more efficiently by tumour cells via clathrin-mediated endocytosis — a key cellular uptake mechanism — allowing them to effectively reach the mitochondria.
