Small interfering RNAs (siRNAs) are novel therapeutics that can be used to treat a wide range of diseases. This has led to a growing demand for selective, efficient, and safe ways of delivering siRNA in cells. Now, in a cooperation between the Universities of Amsterdam and Leiden, researchers have developed dedicated molecular nanocages for siRNA delivery. In a paper just out in the journal Chem they present nanocages that are easy to prepare and display tunable siRNA delivery characteristics.
The researchers were motivated by the potential of siRNA in gene therapy, which requires the need for effective delivery systems. They set out to develop nanocages with functional groups at the outside, making the cages capable of binding siRNA strands. As the binding is based on reversible bonds, the siRNA can in principle be released in a cellular environment. To explore the delivery characteristics of their nanocages, the researchers performed a laboratory study using various human cancer cells.
A range of nanocages
The nanocages are constructions of small molecular building blocks, so-called ditopic ligands, that are connected using metal atoms. A typical cage consists of 12 metal atoms and 24 ligands, hence the abbreviation M12L24. The researchers designed and synthesized five different ligands to form molecular cages with different siRNA binding affinities. They then prepared a range of siRNA binding nanocages using platinum or palladium as connecting metal. The palladium nanocages are less stable in a cellular environment, and decomposition is one of the siRNA releasing mechanisms.
After screening nanocage characteristics such as stability and siRNA binding capability, the delivery characteristics were put to the test in assays based on siRNA-mediated Green Fluorescent Protein (GFP) silencing. The cages were used to deliver siRNA to human GFP-expressing cells, so that fluorescence measurements could establish successful siRNA delivery. Two types of human cell lines were used: HeLa and U2Os.
Cage composition determines siRNA delivery
To their surprise, the researchers could not only demonstrate satisfying siRNA delivery, but also discovered a remarkable differentiation depending on the metal used in the nanocage. Where a platinum-based Pt12L24 nanocage showed highly effective siRNA delivery to U2OS cells, it showed little efficiency for HeLa. By contrast, the palladium-based Pd12L24 nanocage, derived from the same ligand building block, delivered siRNA to HeLa but not to U2OS. Such differentiation could not be observed in experiments were a commercially applied delivery system (lipofectamine) was used. The M12L24 nanocages thus introduce the possibility of tuning siRNA delivery characteristics by tuning the nanocage composition.
News
Microplastics Are Invading Our Arteries, and It Could Be Increasing Your Risk of Stroke
Higher levels of micronanoplastics were found in carotid artery plaque, especially in people with stroke symptoms, suggesting a potential new risk factor. People with plaque buildup in the arteries of their neck have been [...]
Gene-editing therapy shows early success in fighting advanced gastrointestinal cancers
Researchers at the University of Minnesota have completed a first-in-human clinical trial testing a CRISPR/Cas9 gene-editing technique to help the immune system fight advanced gastrointestinal (GI) cancers. The results, recently published in The Lancet Oncology, show encouraging [...]
Engineered extracellular vesicles facilitate delivery of advanced medicines
Graphic abstract of the development of VEDIC and VFIC systems for high efficiency intracellular protein delivery in vitro and in vivo. Credit: Nature Communications (2025). DOI: 10.1038/s41467-025-59377-y. https://www.nature.com/articles/s41467-025-59377-y Researchers at Karolinska Institutet have developed a technique [...]
Brain-computer interface allows paralyzed users to customize their sense of touch
University of Pittsburgh School of Medicine scientists are one step closer to developing a brain-computer interface, or BCI, that allows people with tetraplegia to restore their lost sense of touch. While exploring a digitally [...]
Scientists Flip a Gut Virus “Kill Switch” – Expose a Hidden Threat in Antibiotic Treatment
Scientists have long known that bacteriophages, viruses that infect bacteria, live in our gut, but exactly what they do has remained elusive. Researchers developed a clever mouse model that can temporarily eliminate these phages [...]
Enhanced Antibacterial Polylactic Acid-Curcumin Nanofibers for Wound Dressing
Background Wound healing is a complex physiological process that can be compromised by infection and impaired tissue regeneration. Conventional dressings, typically made from natural fibers such as cotton or linen, offer limited functionality. Nanofiber [...]
Global Nanomaterial Regulation: A Country-by-Country Comparison
Nanomaterials are materials with at least one dimension smaller than 100 nanometres (about 100,000 times thinner than a human hair). Because of their tiny size, they have unique properties that can be useful in [...]
Pandemic Potential: Scientists Discover 3 Hotspots of Deadly Emerging Disease in the US
Virginia Tech researchers discovered six new rodent carriers of hantavirus and identified U.S. hotspots, highlighting the virus’s adaptability and the impact of climate and ecology on its spread. Hantavirus recently drew public attention following reports [...]
Studies detail high rates of long COVID among healthcare, dental workers
Researchers have estimated approximately 8% of Americas have ever experienced long COVID, or lasting symptoms, following an acute COVID-19 infection. Now two recent international studies suggest that the percentage is much higher among healthcare workers [...]
Melting Arctic Ice May Unleash Ancient Deadly Diseases, Scientists Warn
Melting Arctic ice increases human and animal interactions, raising the risk of infectious disease spread. Researchers urge early intervention and surveillance. Climate change is opening new pathways for the spread of infectious diseases such [...]
Scientists May Have Found a Secret Weapon To Stop Pancreatic Cancer Before It Starts
Researchers at Cold Spring Harbor Laboratory have found that blocking the FGFR2 and EGFR genes can stop early-stage pancreatic cancer from progressing, offering a promising path toward prevention. Pancreatic cancer is expected to become [...]
Breakthrough Drug Restores Vision: Researchers Successfully Reverse Retinal Damage
Blocking the PROX1 protein allowed KAIST researchers to regenerate damaged retinas and restore vision in mice. Vision is one of the most important human senses, yet more than 300 million people around the world are at [...]
Differentiating cancerous and healthy cells through motion analysis
Researchers from Tokyo Metropolitan University have found that the motion of unlabeled cells can be used to tell whether they are cancerous or healthy. They observed malignant fibrosarcoma [...]
This Tiny Cellular Gate Could Be the Key to Curing Cancer – And Regrowing Hair
After more than five decades of mystery, scientists have finally unveiled the detailed structure and function of a long-theorized molecular machine in our mitochondria — the mitochondrial pyruvate carrier. This microscopic gatekeeper controls how [...]
Unlocking Vision’s Secrets: Researchers Reveal 3D Structure of Key Eye Protein
Researchers have uncovered the 3D structure of RBP3, a key protein in vision, revealing how it transports retinoids and fatty acids and how its dysfunction may lead to retinal diseases. Proteins play a critical [...]
5 Key Facts About Nanoplastics and How They Affect the Human Body
Nanoplastics are typically defined as plastic particles smaller than 1000 nanometers. These particles are increasingly being detected in human tissues: they can bypass biological barriers, accumulate in organs, and may influence health in ways [...]
