Objective: To investigate the hyaluronic acid (HA) modified, doxorubicin (DOX) and gallic acid (GA) co-delivered lipid-polymeric hybrid nano-system for leukemia therapy.
Methods: We produced a kind of lipid-polymer hybrid nanoparticle (LPHN) with a core-shell structure in which DOX and GA were co-loaded. In vitro and in vivo leukemia therapeutic effects of the HA modified, DOX and GA co-delivered LPHNs (HA-DOX/GA-LPHNs) were evaluated in DOX resistant human HL-60 promyelocytic leukemia cells (HL-60/ADR cells), DOX resistant human K562 chronic myeloid leukemia cells (K562/ADR cells), and HL-60/ADR cells bearing mouse model.
Results: The sizes and zeta potentials of HA modified LPHNs were about 160 nm and −40 mV. HA-DOX/GA-LPHNs showed the most prominent cytotoxicity and the best synergistic effect was obtained when DOX/GA ratio was 2/1. In vivo studies revealed that HA-DOX/GA-LPHNs inhibited tumor growth from 956 mm³ to 213 mm³, with an inhibition rate of 77.7%.
Conclusion: In summary, the study showed that HA-DOX/GA-LPHNs can be applied as a promising leukemia therapy system.
Keywords: acute myeloid leukemia, doxorubicin, gallic acid, multidrug resistance, lipid-polymer hybrid nanoparticles