Abstract
In the study, poly(□-glutamic acid) (□-PGA) and poly(lactide) (PLA) were used to synthesize block copolymers via a simple coupling reaction between □-PGA and PLA to prepare self-assembled nanoparticles (NPs). For the potential of targeting liver cancer cells, galactosamine was further conjugated on the prepared nanoparticles (Gal-NPs) as a targeting moiety. The prepared NPs had a mean particle size of about 140 nm with a zeta potential of about -20 mV. The results obtained by the TEM and AFM examinations showed that the morphology of the prepared NPs was spherical in shape with a smooth surface. Additionally, it was found that no aggregation or precipitation of NPs was observed during storage for up to 1 month, as a result of the electrostatic repulsion between the negatively charged NPs. Moreover, in the cellular uptake study, it was found that the Gal-NPs prepared in the study had a specific interaction with HepG2 cells via ligand-receptor recognition. In the paclitaxel encapsulation study, with an increase of the paclitaxel/polymer ratio form 0.5/10 to 3/10, the mean particle size of the prepared NPs increased from 115 to 260 nm, while the loading efficiency decreased from 76% to 21%. In the in vitro cell viability study, the dose dependent tendency of cytotoxicity for the paclitaxel-loaded Gal-NPs was comparable with that of Taxol□ formulation, and was significantly greater than that of the paclitaxel-loaded NPs. It was found by the immunocytochemistry and flow cytometric studies that the paclitaxel released from the prepared NPs or Gal-NPs could arrest cellular microtubules and altered HepG2 cells in specific cell cycle stages. The biodistribution study in normal or hepatoma tumor-bearing nude mice showed that the Gal-NPs were accumulated mainly in the liver. In contrast, the NPs were distributed mainly in spleen. Additionally, the cumulative amount of the Gal-NPs in the tumor site was considerable greater than that of the NPs. It was noted in the in vivo anti-tumor study that only the paclitaxel-loaded Gal-NPs could significantly reduce the tumor volume and inhibited the tumor growth. Furthermore, the body weight of the paclitaxel-loaded Gal-NPs treated mice were maintained constant. The results indicated that the paclitaxel-loaded Gal-NPs were mainly accumulated in the tumor site due to a higher permeability of tumor vessels and ligand-receptor recognition by hepatoma cells. The aforementioned results indicated that the prepared nanoparticles composed of γ-PGA-PLA block copolymers conjugated with galactosamine may be a potential drug delivery system for targeted delivery to liver cancers or other liver diseases.