Assessment of Nanobiotechnology-Targeted siRNA Designed to Inhibit NF-kappaB Classical And Alternative Signaling in Breast Tumor Macrophages
Abstract
Macrophages have been proposed as a potential target for manipulation of the microenvironment in breast cancer because they are potent effectors of the immune system. NF-kappaB (NF- B) signaling in macrophages contributes to their impact during breast tumorigenesis. Thus, macrophage-targeted modulation of NF- B has potential as a novel therapeutic approach for breast cancer. NF- B signaling is mediated via two major pathways; the canonical/classical pathway and the alternative pathway. Our strategy is designed to develop a nanobiotechnology-based method to target siRNA designed to inhibit NF- B classical and alternative signaling specifically to tumor associated macrophages to modulate the tumor microenvironment and to test the therapeutic potential of this approach. In this highly collaborative study, we have synthesized and characterized in vitro both mannosylated and untargeted nanoparticles. We have compared the efficiency of transfection of bone marrow derived macrophages between nanoparticles and commercial transfection reagents. We have started to investigate the effects of modulation of the NF- B pathways on macrophage phenotype. Finally, we have performed initial in vivo studies that suggest that tumor associated macrophage specific targeting will be feasible in the context of primary tumors and metastases in the lung.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2012
- Accession Number
- ADA590801
Entities
People
- Fiona E. Yull
Organizations
- Vanderbilt University