The unexpected role of FDA-approved drugs in making nanoparticles safer

An international team of researchers, led by scientists at the University of Colorado Anschutz Medical Campus, has identified a new strategy to reduce harmful immune responses triggered by nanomedicines – by using drugs already approved by the FDA for unrelated conditions.

Published in Science Advances, the study shows that certain immune-modulating medications can prevent the body from mistakenly identifying therapeutic nanoparticles as threats.

“Nanoparticles are powerful tools in medicine, but the body often recognises them as threats,” said Dr Dmitri Simberg, co-director and professor at the Colorado Center for Nanomedicine and Nanosafety at the Skaggs School of Pharmacy and Pharmaceutical Sciences at CU Anschutz. “We found that certain existing drugs used for immune-related conditions can help mitigate these reactions.”

Immune system: a double-edged sword

While nanoparticles are engineered to deliver treatments precisely, they can sometimes produce unwanted immune responses. The key culprit is the complement system – a group of proteins in the blood that serve as the immune system’s early warning mechanism.

“This system is crucial for fighting infections, but it can become overactive in response to nanomedicine,” Simberg explained.

Such overactivity may lead to a range of side effects, including inflammation, skin rashes, respiratory issues, cardiovascular problems and even life-threatening anaphylaxis.

Iptacopan shows strong results

To counter these risks, the researchers screened a panel of immune-modulating drugs to see if they could inhibit the complement system without compromising overall immunity. Among the medications tested, iptacopan stood out.

“We were impressed by how well iptacopan performed in preclinical animal models and some human samples,” Simberg said. “It not only reduced immune responses but also prevented more severe symptoms.”

Iptacopan is already approved to treat certain rare disorders affecting the blood, kidneys and nerves. Its effectiveness in reducing complement activation could support its use as an add-on to nanoparticle-based therapies.

Toward personalised nanomedicine

The study also found that patients respond differently to nanomedicine, depending on factors such as the type of nanoparticles used and individual biological variability. This discovery strengthens the need for a tailored approach to treatment.

“We still need to understand which patients are at higher risk of allergic or inflammatory reactions, in order to apply immune modulating drugs during nanomedicine treatment,” Simberg added.

Expanding the reach of nanotherapy

By reducing adverse immune reactions, the study could lead to wider and safer use of nanomedicine across a range of different diseases.

“If we can manage the body’s response more effectively, we can improve access to these life-saving therapies for a wider group of patients,” said Simberg.