Professor pioneers spleen-targeted drug delivery system for lupus
Strategy aims to selectively suppress disease-driving cells
An associate professor of biomedical engineering at the University of Houston is developing a new way to deliver treatments for lupus directly to the spleen, which is the home of certain immune cells thought to drive the disease’s progression.
Tianfu Wu, PhD, is working on an experimental approach that uses tiny fat-based carriers, called lipid nanoparticles, that are coated with mannose, a natural sugar that binds to receptors on splenic immune cells and guides the particles directly to their targets. This targeted strategy aims to selectively suppress disease-driving cells, while leaving the rest of the immune system intact, thereby overcoming risks and limitations of current therapies.
Backed by a $1 million Impact Award from the U.S. Department of Defense — a competitive grant that supports bold, high-impact medical research — Wu’s work is believed to be the first attempt to design a drug delivery system that specifically targets the spleen in lupus.
“The current therapeutic landscape for lupus is often marred by systemic side effects and relatively limited efficacy,” Wu said in a university news story. “To address these challenges, we are proposing a spleen-specific selective organ-targeting lipid nanoparticle drug delivery system to modulate immune responses and mitigate symptoms with minimal side effects.”
Focusing on spleen could yield new insights into how lupus develops
Lupus is a chronic autoimmune disease in which B-cells — a type of immune cells that normally produce antibodies to help fight off infections — start producing autoantibodies that mistakenly attack the body’s healthy tissues. This, in turn, activates other immune cells, such as dendritic cells and macrophages, which release inflammatory signals to perpetuate a cycle of immune activation and organ damage. Symptoms range from fatigue and joint pain to severe complications affecting the kidneys, heart, and nervous system.
To control symptoms, existing treatments often broadly suppress the immune system or lower the number of B-cells. These approaches, however, can compromise overall immunity and raise the risk of infections and other complications.
“New drug delivery systems are urgently needed to provide more effective treatment options that fine-tune or modulate the immune system rather than employing systemic immunosuppression or B-cell depletion,” Wu said. “[Broad] immunosuppression can lead to severe side effects and increase the risk of infections, while [broad] B-cell depletion may wipe out beneficial B cells, leading to unfavorable complications.”
In lupus, the spleen — normally responsible for filtering blood and orchestrating immune defenses — becomes a hub of overactive B-cells, macrophages, and dendritic cells. By homing in on this organ, Wu’s strategy could directly interrupt the source of inflammation rather than suppressing the entire immune system.
Importantly, Wu notes, focusing on the spleen may not only advance treatment options, but also uncover new insights into how lupus develops.
“Significantly, this innovation will pave the way for treating lupus by targeting organ-specific molecular pathways, recognizing that the same drug target may have opposing roles in different organs, such as the spleen versus end-organs like the kidney, heart, or central nervous system,” Wu said.
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