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Repurposed Immune-Modulating Drugs Could Make Nanomedicines Safer

A lipid nanoparticle containing mRNA vaccine approaches a cell membrane.
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An international study led by researchers at the University of Colorado Anschutz Medical Campus has identified a promising strategy to enhance the safety of nanomedicines, advanced therapies often used in cancer and vaccine treatments, by using drugs already approved by the FDA for unrelated conditions.


The study was published today in Science Advances.


Their research suggests that repurposing existing medications can reduce harmful immune responses associated with nanoparticles. These ultra-small particles are designed to deliver treatments with precision but, in some cases, the immune system can react adversely.

'Nanoparticles are powerful tools but the body often recognizes them as threats'

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


When introduced into the body for therapy or imaging, nanoparticles can trigger inflammation and other immune-related side effects. This occurs when the immune system, particularly the complement system, a group of blood proteins responsible for detecting potential threats, mistakenly targets helpful nanoparticles.


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


These overreactions may cause symptoms such as skin rashes, respiratory distress, cardiovascular problems or serious anaphylactic reactions. To address this, the team tested immune-modulating compounds that inhibit complement activation, aiming to reduce immune attacks on nanoparticles without broadly weakening the immune system.

'Iptacopan was notably effective in blocking complement activity and minimizing adverse effects'

Among the drugs tested in blood samples, iptacopan, currently approved to treat certain rare blood, nerve, and kidney disorders, was notably effective in blocking complement activity and minimizing adverse effects.


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


The researchers also noted considerable variability in how individuals respond to nanoparticle-based treatments, often depending on specific ingredients used. This highlights the importance of personalized approaches to nanomedicine.


“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.


Simberg said the findings open the door to broader and safer applications of nanomedicine for diseases such as cancer, infections and genetic conditions.


“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.


Reference: Li Y, Jacques S, Gaikwad H, et al. Enhanced immunocompatibility and hemocompatibility of nanomedicines across multiple species using complement pathway inhibitors. Sci Adv. 11(28):eadw1731. doi: 10.1126/sciadv.adw1731


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