How can a drug be released or activated exactly where and when it is needed in the body? For many treatments, particularly in cancer therapy, the active compound should ideally act only at a specific site. Yet in practice, drugs are distributed throughout the entire body: the disease is local, but the therapy is systemic, with little spatial or temporal control.
Researchers at TU Wien have now taken an important technological step forward by combining electronic ion pumps with so-called click-to-release chemistry. Ion pumps can deliver small charged molecules on demand with high precision, but until now they have been limited to relatively small compounds. The new approach overcomes this limitation: instead of transporting the drug itself, small “chemical scissors” are delivered, which release previously immobilized drugs directly at the target site. This enables, for the first time, the precise electronic control of drug release for a much broader range of therapeutics. Several patents have already been filed, and the “iontronic click-to-release” technology has now been published in the journal Nature Communications .
Ion pumps: delivering molecules at the push of a button
“When a drug is taken orally or injected, it spreads throughout the entire body. Only a tiny fraction, roughly one millionth, reaches the site where it is actually needed, for example tumor cells,” says Johannes Bintinger from the Institute of Applied Synthetic Chemistry at TU Wien, who led the project.
Ion pumps, originally developed at Linköping University in Sweden, offer a solution. These are small electronic devices that are intended to be implanted directly into the body. Inside the device, an ion-selective membrane and an applied electrical potential enable charged molecules to be transported and released in a controlled and time-resolved manner, directly at the site of the implant. In this way, the release of substances can be precisely controlled at the push of a button.
“However, there is a fundamental limitation,” explains Sebastian Hecko (TU Wien), first author of the study. “Ion pumps are not suitable for every molecule. They can only deliver electrically charged compounds below a certain size.”
This excludes many important drugs, particularly large biomolecules such as proteins, which are too bulky to pass through the membrane. “This is where the second part of our research comes into play,” says Johannes Bintinger: “click-to-release chemistry.”
Click-to-release: precise activation at the target site
Click-to-release chemistry is a concept from bioorthogonal chemistry. It refers to highly selective reactions between specifically designed molecular partners that proceed without interfering with other molecules in the body.
In this approach, drug molecules are bound to a local depot via cleavable chemical linkers and remain immobilized. “Only a suitable trigger molecule can break this bond and release the drug at the desired location. This is exactly the principle we combine with the ion pump: instead of transporting the drug itself, we deliver a small trigger molecule that selectively cleaves locally immobilized drug conjugates. This allows precise control over both the timing and the dose of drug release,” explains Hannes Mikula (TU Wien).
“We were able to demonstrate that ion pumps can be used to electronically control the release of such trigger molecules with high precision,” says Sebastian Hecko. “This allows us to determine exactly when and how much drug is released at the target site. In doing so, we have functionally integrated two complementary technologies and combined their respective strengths.”
Targeted local therapy instead of systemic exposure
Because drugs are activated precisely where they are needed, significantly lower doses can be sufficient, which greatly reduces side effects. This is particularly relevant for patients with localized diseases, who often still receive systemic therapies such as chemotherapy.
“A single drop can contain far more of a drug than is needed for several weeks of cancer treatment,” says Johannes Bintinger. “At the same time, the electronically controlled ion pump allows precise regulation of drug release. Some drugs are most effective when administered at a specific time of day. With an ion pump, this is straightforward, whereas with conventional methods such as pills or infusions, it is practically impossible.”
The study, conducted by researchers from TU Wien, Linköping University, and the Medical University of Graz, demonstrates through experiments with living cells that the new method is highly precise and reliable. Further studies are now planned to advance the technology toward clinical application. “There are many potential medical applications,” says Johannes Bintinger. “Our goal is to translate this technology into concrete therapeutic solutions.”
Nature Communications
Experimental study
Not applicable
Iontronic click-to-release enables electrically controlled delivery of drugs and biomolecules beyond charge and size limitations.
17-Mar-2026