Nanomedicine has long suffered from a throughput problem. Candidate particle designs must be tested in living systems one at a time, which makes systematic exploration of size, shape and surface chemistry prohibitively slow and animal-intensive. A team from the NUS Department of Biomedical Engineering and the Institute for Health Innovation and Technology addressed this by tagging each gold nanoparticle design with a unique DNA sequence, so that many designs can be followed simultaneously.
Thirty designs were tracked at once in tumour-bearing preclinical models, with next-generation sequencing reading out where each barcode accumulated. The approach generated more than 1,000 in vivo data points while requiring roughly thirty times fewer animals than one-by-one screening. It also surfaced a general pattern: particles that accumulated well in tumours were also more likely to reach mitochondria, the organelles that supply a cancer cell's energy and a target of growing therapeutic interest.
One design stood out. A folic-acid-modified cubic gold nanoparticle achieved 99 per cent tumour regression in preclinical studies when combined with mitochondria-targeted RNA therapy and mild photothermal therapy. The study appeared in Advanced Materials. The combination matters as much as the particle, since reaching the mitochondrion is only useful if a payload capable of acting there arrives with it.
For the wider field the methodological point outweighs the individual result. Barcoded pooled screening transformed genomics and later immunology by replacing sequential testing with parallel measurement. Extending it to nanoparticle pharmacokinetics offers a route to design rules grounded in data rather than in trial and error, and incidentally reduces the animal burden that has made such studies ethically as well as practically constrained.