The use of nanocarriers in acute myeloid leukaemia therapy: challenges and current status.

Chemotherapy for AML is hampered by severe side-effects and failure to eliminate all the blasts that eventually leads to relapse. The use of nanosized particulate drug carriers such as liposomes and polymeric nanoparticles has the potential to improve AML therapy by delivering more of the drug to the disease site, thereby reducing toxicity. For example, encapsulation in liposomes reduces the cardiotoxicity of anthracyclines, giving an improved therapeutic index. Moreover, when the surface properties are engineered appropriately, nanocarriers remain in the circulation and extravasate in tissues with sinusoidal capillaries, one of which is bone marrow, leading to a more favourable distribution of the associated drug. Drug carrier technology contributes to the development of newer drugs, such as nucleic acids that can be protected from degradation and delivered into cells, thus opening the way for gene-silencing strategies. Furthermore, carrier systems provide a means of dispersing poorly water-soluble molecule for in vivo administration and thus increase the "druggability" of new lead compounds, such as heat-shock protein inhibitors. Particulate carriers can transport more than one active agent, allowing synergistic action and theranostic strategies. Notably, phase I and II clinical trials are being performed with CPX-351, a liposomal formulation containing cytarabine and daunorubicin at an optimal ratio. Finally, by attaching suitable ligands to the nanocarrier surface, specific targeting to AML cells can be achieved. In this review, we give examples of successful targeting to folate and transferrin receptors against AML.