Application of gold nanoparticles in the treatment of B-Chronic Lymphocytic Leukemia (CLL)
Priyabrata Mukherjee, Ph.D.
Mayo Clinic
Abstract:
Background and Rationale: Angiogenesis play a crucial role in the survival of CLL B cells. Abnormal angiogenesis was found in marrow sections of B-CLL patients and significantly higher levels of bFGF and VEGF in the urine of B-CLL patients. In support, it was found that abnormal marrow angiogenesis was positively associated with advancing stage of CLL. In addition, it is also found that a VEGF based pathway can generate signals that lead to increased resistance to both spontaneous and drug induced apoptosis in CLL. Preliminary work has indeed shown that we can induce a significant apoptosis with a variety of anti-angiogenic agents but we wish to increase the ability to do this with use of more advanced effective delivery systems. To do this we have now focused on the new technology of nanoscience.
Advantage of Nanotechnology: Nanotechnology has the potential to change the very foundation of cancer treatment, detection and diagnosis. The primary rational for selecting gold nanoparticles is their biocompatibility, very high surface area so that multiple drugs can be loaded, ease of characterization and surface functionalization (easy to tether molecules of choice on the surface). When the drugs/antibodies will be delivered as nanoconjugates, they will have better efficacy with reduced toxicity.
Preliminary Results: In our preliminary studies we have seen significant enhancement (2-10 fold) in apoptosis induced by gold v-EGF antibody conjugates compared to VEGF antibody alone (N=5).
Specific Aims: In conjunction with our preliminary results, our specific aims would include to test:
The effect of gold nanoparticles of different sizes to kill CLL-B cells.
The effect of gold-AVF nanoconjugates to kill the CLL-B compared to only AVF and finding out the mechanism of such activity.
The effect of gold-AVF bioconjugates in combination with chemotherapeutic agents to kill the CLL-B cells and elucidate the mechanism of action.