Size-controlled D-Mannose-Conjugated Polymeric Micelles For Targeted Drug Delivery

Tumor is the most dangerous disease in the world, and chemotherapy is one of the most effective methods to treat tumor. Nowadays, there are about 500 antitumor drugs in the clinic, but the mortality rate of tumor is still up to 20%. Two main reasons lead to the high mortality rate, the harmful side effects of drugs and the multidrug resistance of tumor cells. To decrease the side effects and increase the therapeutic effects, scientists have paid a great effort on it for years. With the fast development of nanotechnology, the researches of targeted drug delivery systems based on nano-sized vehicles have been the most attractive field. There are kinds of nano-sized vehicles, amid those vehicles, polymeric micelles play a very significant part in nanomedicine field, because they are easy to synthesized, decorated and controlled size. In recent years, various smart drug delivery systems have been developed by decorating polymeric micelles.In this study, D-mannose-conjugated amphilic polymer(PSA-b-PGMA-Mannose) was synthesized and used to prepare polymeric micelles with size-controlled and mannose-mediated targeting property. DOX, a hydrophobic antitumor drug, was encapsulated into the micelles by oil-water method. Structures of PSA-b-PGMA-Mannose was confirmed by FT-IR and 1H NMR. The sizes and morphologies of different hydrophilic/hydrophobic block ratios of PSA-b-PGMA-Mannose were characterized by transmission electron microscopy and dynamic light scattering. The results showed a decrease in the average size of polymeric micelles upon an increase in the hydrophilic/hydrophobic block ratio.DOX-loaded polymeric micelles(DOX@PSA-b-PGMA-Mannose) were prepared by dislysis method. The encapsulation efficiency(EE) and the DOX-loading content(DLC) were measured by fluorescence spectrophotometer. Using mannose-receptor-over-expressing MDA-MB-231 cells and mannose-receptor-poor HEK293 cells as model tumor and normal cells respectively, the in vitro cellular uptake and cytotoxic effect of the micelles were evaluated by confocal laser scanning microscopy and MTT assay. The results showed that DOX-loaded micelles were efficiently trapped by MDA-MB-231 tumor cells through receptor-mediated endocytosis, while HEK293 cells showed much lower endocytosis. DOX@PSA-b-PGMA-Mannose have a great tumor growth-inhibition effect in vitro on MDA-MB-231 tumor cells compared with that of DOX. In conclusion, our prepared DOX@PSA-b-PGMA-Mannose showed high anti-tumoral efficacy and low toxicity, thus it has the potential to develop as an effective drug delivery system and applied in cancer therapy.