In vitro and in vivo effect of hyaluronic acid modified, doxorubicin and gallic acid co-delivered lipid-polymeric hybrid nano-system for leukemia therapy

Abstract

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

Acknowledgment

The work was supported by the Taizhou Science and Technology Bureau (No. 162yw01): Study on the Jak-stat pathway mediated HLX regulation of AML cell carcinogenesis and mechanism.

Disclosure

The authors report no conflicts of interest in this work.