Will synthetic cells soon offer new solutions for producing and delivering drugs in the body?
Note: In this article, we use the term ‘synthetic cell’ to refer to any cell-sized compartment with minimal cellular functionality, such as protein synthesis.
British researchers have successfully developed simple cell mimics that activate only when exposed to a magnetic stimulus. Magnetic fields can penetrate deep into body tissue and, in this specific case, were used at intensity and frequency levels that are safe for humans. This work opens up new possibilities for programming synthetic cells to produce/transport drugs and release them in a controlled manner within the body.
Biodegradable polymers, artificial photosynthesis to capture CO₂, biosensors, new drug delivery systems capable of treating conditions by producing and releasing molecules on demand within the body. The list of possible applications arising from synthetic cell research promises to make a profound impact on our society. But scientists face many obstacles in bringing them to fruition.
For example, programmability is a prerequisite for drug delivery systems. However, until now, no study had demonstrated the possibility of designing programmable synthetic cells capable of producing and/or releasing drugs into the body on demand and in a way that is safe for the body.
Researchers at University College London (UCL) and the University of Oxford have made a breakthrough in this area. They have developed a system that can be remotely activated by a magnetic stimulus at levels of intensity and frequency that are safe for humans.
“Magnetism is one of only a few stimuli that can penetrate body tissue. That’s where the interest lies,” explained researcher Michael Booth, who initiated the project.
What they achieved: remote activation of DNA and protein production in a cell mimic
The researchers drew inspiration from spherical nucleic acids (SNAs) to build their cell-like system. They radially attached double-stranded DNA around tiny magnetic iron oxide nanoparticles and enclosed them, along with a free inactive DNA template, within a lipid membrane.
When an alternating magnetic field was applied, the magnetic nanoparticles heated up and released the DNA. This DNA contained a promoter — a DNA sequence that acts as an ‘ON’ switch — which, once released, hybridised with the inactive DNA template and initiated protein synthesis.
“The idea was not easy to implement, as it requires a wide range of skills — in inorganic chemistry, nucleic acid chemistry, cell-free synthetic biology, synthetic cell engineering — which not everyone necessarily possesses, but our group does,” explained Michael.
First, the researchers tested their system using DNA that encodes a fluorescent protein. They conducted the experiment and observed their so-called ‘synthetic cells’ glowing green when exposed to a magnetic stimulus. Next, they showed that the synthetic cells could be activated by a magnetic field even when they were inside a black tube, used to mimic the hard tissue of a living organism. Finally, to showcase the flexibility of their design, they encapsulated a DNA template encoding a pore-forming protein along with small fluorescent molecules. When exposed to magnetic stimuli, the proteins formed pores, making the membrane of the synthetic cells porous and releasing the fluorescent molecules.
Overcoming premature leakage: a major design challenge
To firmly bind the DNA to the surface of the magnetic nanoparticles, the research team used click chemistry, where molecules click together like LEGO bricks.
However, some DNA remained only loosely bound to the nanoparticles, meaning they came off too easily and leaked into the environment.
To combat this, the team developed a new method to pull off the loosely bound DNA strands. They embedded the nanoparticles in a gel and applied an electric field. As DNA is highly electrically charged, the loosely bound strands moved away from the particles, leaving in place only strands that were firmly attached.
This new technique reduced the amount of “leaky” DNA by 90%, the researchers calculated.
Implications for drug delivery and therapeutic applications
“What is exciting about our study is that it opens up the potential for synthetic cells to be used in the body. It makes new kinds of treatments possible,” said Michael.
“Synthetic cells can be customised for a wide range of uses. They could in future be engineered to release a medicine upon detecting something in their immediate environment – say, a tumour or bacteria. This more targeted approach could allow clinicians to use smaller doses of a treatment, making it safer.”
This localised heating of a magnetic nanoparticle, triggered by an alternating magnetic field, is already used to treat glioblastomas, a type of brain cancer. “Our proof of principle opens up the possibility of repurposing an already clinically approved therapy for killing cancer cells by utilising alternating magnetic fields to make and release drugs only in the target area inside the body,” added first author Ellen Parkes.
“The approach, using synthetic cells, is versatile and will enable different drugs that target a range of cancers to be made. This technology has the potential to become a new type of therapy with further research underway in a cancer model,” she continued.
What are the next steps for Michael’s group?
The team is currently modifying the system to enhance its suitability for drug delivery.
“Our proof-of-principle work was carried out in water and the next step is for this technique to be tested with an anti-cancer ‘cargo’ targeting cancer cells in the lab,” said Michael.
In addition, they plan to test the stability of their system in a tissue model and evaluate its activity in vivo in more detail.
Scientific publication
Magnetic activation of spherical nucleic acids enables the remote control of synthetic cells
Ellen Parkes, Assala Al Samad, Giacomo Mazzotti, Charlie Newell, Brian Ng, Amy Radford and Michael J. Booth
Nature Chemistry (2025)
Press release from University College London
Synthetic cells could be a new way to deliver drugs in the body
