Novel Curcumin Liposome Modified with Hyaluronan Targeting CD44 Plays an Anti-Leukemic Role in Acute Myeloid Leukemia in Vitro and in Vivo

Curcumin has been widely used as a food additive for centuries and has been recently explored for its anti-inflammatory and antitumor properties. Although curcumin is pharmacologically safe and efficacious to certain cancers, its role against acute myeloid leukemia (AML) still remains unclear, and it lacks clinical application due to low water solubility and low in vivo bioavailability. To address these issues, we developed a novel curcumin liposome modified with hyaluronan,(HA-Cur-LPs) to specifically deliver curcumin to AML by targeting CD44 on AML cell surface. When compared with free curcumin and nontargeted liposome (Cur-LPs), the HA-Cur-LPs exhibited good stability, high affinity to CD44, increased cellular uptake, and more potent activity on inhibiting AML cell proliferation. The KG-1 cell implanted AML mice had significantly delayed, or even prevented, AML progression following treatment with 50 mg/kg of curcumin dose in the HA-Cur-LPs every 2 days for 2 weeks. Mechanistically, the anti-AML effects of HA-Cur-LPs were achieved by inhibiting Akt/ERK pathways and activating caspase-dependent apoptosis. Moreover, HA-Cur-LPs played a critical role in downregulation of DNMT1 expression in AML, leading to DNA hypomethylation and reactivation of tumor suppressor genes such as miR-223. The development and assessment of the HA-Cur-LPs in this study provide another potential choice for AML therapy, using HA-Cur-LPs as either a single treatment agent or in combination with other treatments.