PEGylated chitosan-based polymer micelle as an intracellular delivery carrier for anti-tumor targeting therapy.

Stearic acid-grafted chitosan oligosaccharide (CSO-SA) micelles presented a potential candidate for intracellular drug delivery carrier due to its special spatial structure. In this article, CSO-SA was further modified by polyethylene glycol (PEG). The physicochemical properties of PEGylated CSO-SA (PEG-CSO-SA) micelles were characterized. After PEGylation, the critical micelle concentration (CMC) of PEG-CSO-SA had no significant change; the micelle size increased; and the zeta potential decreased. The cellular uptake of CSO-SA micelles before and after PEGylation in macrophage RAW264.7, immortalized rat liver cells BRL-3A and human liver tumor cells HepG2 was studied. About 58.4+/-0.63% of CSO-SA micelles were uptaked by RAW264.7 in 24h, however, only 17.7+/-0.94% of PEG-CSO-SA micelles were internalized into RAW264.7 after the CSO-SA was modified with PEG in five molar times. Meanwhile, there were no changes in the uptake after PEGylation of CSO-SA in BRL-3A and HepG2. Using mitomycin C as a model drug, the in vitro anti-tumor activities of the drug loaded in the micelles were investigated. The 50% cellular growth inhibition (IC(50)) of the drug decreased from 1.97+/-0.2 to 0.13+/-0.02mug/mL after mitomycin C was loaded into CSO-SA micelles, and the IC(50) value of the drug had no obvious change when the CSO-SA was modified by PEG.