Functional alginate nanoparticles for efficient intracellular release of doxorubicin and hepatoma carcinoma cell targeting therapy.

In order to efficiently deliver chemotherapy drugs into hepatoma cells, a pH-sensitive and liver-targeted drug delivery system (glycyrrhetinic acid-modified alginate/doxorubicin-modified alginate complex nanoparticles), termed GA-ALG/DOX-ALG NPs, was prepared. First, GA-ALG and DOX-ALG were synthesized, and then GA-ALG/DOX-ALG NPs self-assembled by mixing GA-ALG and DOX-ALG via dialysis. Properties of pH-sensitivity, biodistribution in mice, and antitumor activity against ectopic hepatoma tumors in the NPs were evaluated. DOX release from GA-ALG/DOX-ALG NPs showed pH-sensitivity; less than 10% of drugs were liberated at pH 7.4 within 9 d while 58.7% of DOX released at pH 4.0. The confocal laser scanning microscope (CLSM) experiment showed that GA-ALG/DOX-ALG NPs can respond to the endosomal/lysosomal environment and had pH-triggered intracellular releasing property. The area under the curve (AUC(0-∞)) and half-life (t(½)) in the liver of GA-ALG/DOX-ALG NPs were 1156.7 μg h/g and 34.3 h, respectively, which was 11.8- and 3.2-fold higher than that of the DOX·HCl group. Furthermore, the inhibition rate of tumor growth was 79.3% after treatment with GA-ALG/DOX-ALG NPs, which was much higher than that of the DOX·HCl (48.5%) and DOX-ALG NPs groups (62.7%). Importantly, no mice died in the GA-ALG/DOX-ALG NPs group, while the mortality rate was 40% in the DOX·HCl group.