University of Houston biomedical engineer Tianfu Wu has secured a $1 million Impact Award from the U.S. Department of Defense to develop a groundbreaking spleen-targeted drug delivery system for treating systemic lupus erythematosus (SLE). This innovative approach represents what may be the first instance of a spleen-specific targeting system designed, developed and applied in lupus models.
Novel Nanoparticle Design Targets Critical Immune Cells
Wu's system employs lipid nanoparticles modified with mannose, a simple sugar, to deliver medication directly to the spleen where key immune cells drive lupus pathogenesis. The mannose modification facilitates binding to mannose receptors, ensuring precise delivery to splenic immune cells including B cells, plasmacytoid dendritic cells and macrophages.
"The current therapeutic landscape for lupus is often marred by systemic side effects and relatively limited efficacy," said Wu, associate professor of biomedical engineering at UH. "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."
Addressing Limitations of Current Lupus Therapies
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 plays a critical role in lupus development as it houses millions of white blood cells that carry out immune system functions, earning it the designation as the "security guard of the bloodstream."
Current treatment approaches face significant limitations, as Wu explained: "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. 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."
Organ-Specific Therapeutic Strategy
The research aims to advance understanding of lupus pathogenesis while developing more targeted treatment strategies. Wu emphasized the importance of organ-specific approaches, noting that "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."
This spleen-targeted approach represents a significant departure from conventional systemic therapies, potentially offering improved efficacy while minimizing the broad immunosuppressive effects that characterize current lupus treatments.
