New nanoparticle drug delivery system targets the spleen for precise lupus treatment

With a $1 million Impact Award from the U.S. Department of Defense, Tianfu Wu, a University of Houston biomedical engineer, is developing a method to send medication directly to the spleen where certain immune cells cause the disease known as lupus, or Systemic Lupus Erythematosus. 

Lupus is a debilitating autoimmune disease characterized by uncontrolled disease activity, frequent flares, long-term immunosuppression, increasing infection rates, cumulative organ damage and decreased quality of life. 

The spleen has often been called the security guard of the bloodstream, filtering out old or damaged blood cells while housing millions of white blood cells, or lymphocytes, that carry out immune system functions. It is because the spleen harbors these cells it plays a critical role in how lupus develops.

The current therapeutic landscape for lupus is often marred by systemic side effects and relatively limited efficacy. 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."

Tianfu Wu, associate professor of biomedical engineering, University of Houston

Wu's system will use tiny fat-based particles, or lipid nanoparticles, modified with mannose, a simple sugar, to carry medicine directly to the spleen and to target B cells, plasmacytoid dendritic cells and macrophages, which are critical immune cells thought to drive the disease. The use of mannose facilitates the binding to mannose receptors, ensuring precise delivery to these splenic immune cells. 

"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," said Wu. "Systemic immunosuppression can lead to severe side effects and increase the risk of infections, while systemic B-cell depletion may wipe out beneficial B cells, leading to unfavorable complications." 

This work may mark the first instance of a spleen-specific targeting system being designed, developed and applied in lupus models.

"The primary aim is not only to advance treatment strategies for lupus but also to deepen our understanding of lupus pathogenesis. 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," said Wu.