A series of drug delivery systems based on a sodium alginate derivative were prepared by mixing glycyrrhetinic acid (GA) and doxorubicin (DOX) conjugates at different ratios. GA (a liver-targeting ligand) and DOX (an antitumor drug) were both conjugated to oligomeric glycol monomethyl ether-modified sodium alginate (ALG-mOEG) for prolonged duration of action. These NP-based delivery systems exhibited active cell uptake and cytotoxicity

in vitro

and liver-targeted distribution and anti-tumor activity

in vivo

. In addition

nanoparticles with a 1:1 (

W:W

) ratio of GA-ALG-mOEG and DOXALG-mOEG (NPs-3) showed the highest cellular uptake and cytotoxicity

in vitro

and liver-targeted distribution and antitumor activity

in vivo

. Specifically

when mixed nanoparticles defined as NPs-3 were injected in mice

liver DOX concentration reached 61.9 μg/g 3 h after injection

and AUC

0−∞

and

t

1/2

of DOX in liver reached 4744.9 μg·h/g and 49.5 h

respectively. In addition

mice receiving a single injection of NPs-3 exhibited much slower tumor growth (88.37% reduction in tumor weight) 16 days after injection compared with placebo. These results indicate that effective cancer treatment may be developed using mixed NP delivery systems with appropriate ratio of targeted ligand and drug.