Abstract

Mantle cell lymphoma (MCL) is a distinct genetic subtype of B-cell Non-Hodgkin’s Lymphoma. It is genetically characterized by the t(11:14)(q13:q32) translocation leading to a constitutive expression of cyclin D1, facilitating deregulation of cell cycle at G1-S phase transition. There is currently no standard therapy for newly diagnosed or relapsed disease. New treatment approaches are needed that target novel biologic pathways. Since nanotechnology serves as a valuable tool for cancer therapies, we used a formulation of All Trans Retinoic Acid (ATRA)/Curcumin in nanoparticles (termed nanodisks, ND). The nanodisks were scaffolded with a fusion protein comprising scFv against CD20 and apoA1, to provide targeting to the MCL cells which predominantly express CD20. We assessed the relative ability of these novel targeted drug delivery agents to induce apoptosis in MCL, as well as in cells demonstrating a neoplasm of follicle center B (HF-1), using annexin/propidium iodide flow cytometry. Our data show that curcumin-ND induced cell death more effectively than ATRA-ND, or with untreated cells. Furthermore, a combination of curcumin-ND and ATRA-ND enhanced the biological activity of these drugs significantly compared to individual treatments. In summary, we determined the effects on cell death through an effective targeted drug delivery approach, via nanoparticles, to MCL cancer cells.