Scientists call for fresh approach to nanoparticle therapies
Smarter nanoparticle designs and a deeper understanding of their behaviour could make cancer treatments more effective and reliable, according to CEB researchers
Researchers are urging a fresh approach to unlocking the potential of nanoparticles in medicine, with hopes of accelerating the development of smarter, more reliable treatments for cancer, gene therapies, and vaccines.
It is believed that nanoparticles hold huge promise for delivering medicines directly to where they’re needed – reducing side effects and improving outcomes. Yet despite decades of research, many targeted nanoparticle drug delivery systems have fallen short in clinical trials.
Professor Ljiljana Fruk and research associate Dr Andrew Baker are co-first authors from the Department of Chemical Engineering and Biotechnology’s Bionano Engineering Group. In their new opinion article in Materials Horizons, they explain that the current focus on complex ‘active targeting’ strategies often misses the mark. Instead, simpler ‘passive’ nanoparticles, which rely on natural biological processes, often perform just as well or better in patients.
Dr Baker said: “For a long time, people have thought that surface ligands are static, and nanoparticles themselves are biologically inert. However, we and others are noticing that modified nanoparticle can change the protein landscape of the cell sometimes to their own detriment.”
Instead, simpler ‘passive’ nanoparticles, which rely on natural biological processes, often perform just as well or better in patients.
“Sometimes less is more,” said Professor Fruk. “Our work shows that real progress requires understanding how nanoparticles behave in the body – their circulation times, clearance, and interactions with targets – rather than just adding more complicated targeting parts.”
The article draws on examples like the lipid nanoparticles used in COVID-19 vaccines, which naturally accumulate in specific organs without elaborate targeting, and reveals how active targeting can unintentionally reduce target availability, limiting treatment effectiveness.
Published on 25 June 2025, the commentary article – which offers expert insight rather than presenting new experimental results – has also been selected for a future cover of the journal, to be published on 7 September 2025 in print. The cover design was created by Fruk, Baker, and graphic designer David Bainbridge.
Dr Baker said: “By focusing on the biology behind delivery, and embracing simpler, smarter designs, we can speed up development of safer, more effective therapies.”
It follows complementary work from Fruk’s group on nanoparticle-mediated targeted protein degraders (NanoPDs) – an emerging strategy for eliminating disease-linked proteins in cancer and neurodegeneration using nanoparticles.
Their recent review, published in Angewandte Chemie International last month, written by Baker, PhD student Adrian Pui Ting Ho, Itzhaki, and Fruk highlights the promise of NanoPDs in overcoming the limits of small-molecule degraders, and enhancing these reactions using nanomaterials. It also shows promise for targeted nanomaterials and a new avenue for biomedical exploration.
“If we can understand why nanomaterials enhance these degradation reactions, as well as the consequences, we could unlock the next generation of nanomedicine”, Baker added.