The Delivery Problem in Cancer Therapy
The most potent cancer drug is useless if it cannot reach its target. Nanoparticles have long held promise as delivery vehicles, but their journey through the body is fraught with biological barriers: the bloodstream, tumour vasculature, cellular membranes, and intracellular compartments that degrade therapeutic cargo. Screening nanoparticle designs has traditionally been a slow, resource-intensive process, with each formulation tested individually in animal models.
Researchers at the National University of Singapore (NUS) have solved this bottleneck with an elegant innovation: DNA barcoding. By tagging each gold nanoparticle formulation with a unique DNA sequence, the team was able to track and compare dozens of designs simultaneously in living tumour models, rapidly identifying those most effective at reaching mitochondria—the energy centres inside cancer cells. The study, published in Advanced Materials on 17 February 2026, represents a significant leap forward in precision nanomedicine.
From 30 Designs to 1,000 Data Points
The team, led by Assistant Professor Andy Tay from the Department of Biomedical Engineering, tested a library of 30 nanoparticle designs varying in shape, size, and targeting ligands. After administering the pooled nanoparticles to tumour-bearing preclinical models, they analysed distribution from whole organs down to the subcellular level using next-generation sequencing. This multiplexed approach generated more than 1,000 in vivo data points while requiring roughly 30-fold fewer animal models than conventional one-by-one screening.
Among the candidates, a folic acid-modified cubic gold nanoparticle stood out. When combined with mitochondria-targeted RNA therapy and mild photothermal therapy, it achieved 99% tumour regression in preclinical studies.
Why Mitochondria Matter
Mitochondria regulate energy production and programmed cell death—two processes that cancer cells hijack to survive and proliferate. Delivering drugs directly to these organelles can disrupt tumour metabolism and trigger cancer cell death. However, as Asst Prof Tay explained, “Getting nanoparticles to the right place inside the body involves putting them through a complicated obstacle course.” The DNA barcode platform enables researchers to navigate that course with unprecedented efficiency.
The work builds on the team’s earlier 2024 study, which first demonstrated DNA barcoding for tracking nanoparticle biodistribution at the tissue level. The new platform extends the analysis to cellular and subcellular scales, providing a rational framework for designing next-generation precision cancer therapies.
