Evaluation Of Biocompatibility And Antitumor Effect Of PDC-M Nano Micelle

To evaluate the biocompatibility and anti-tumor effect of PDCM nano micelle in vitro and in vivo.The Biocompatibility of PDC-M: The cell viability of PDC-M and DOX in LO2 cells was evaluated by MTT.The organ damage assays were studied in SD rats and performed by evaluating corresponding functional enzymes with fully automatic clinical chemistry and immunoturbidimetric analyzer.The physical stability of PDC-M in the aqueous solution and fetal bovine serum was monitored in terms of the size.Hemolysis activity was investigated of PDC-M and DOX.The results revealed that the resulting PDC-M possesses excellent cell compatibilities and low cytotoxicities in comparison with that of the free DOX.The parameters of PDC-M group substantially maintained at normal levels,indicating that PDC-M did not lead to serious damage in liver,kidney and heart of mice in the treatment duration.The PDC-M have good stability in biological milieu and fetal bovine serum and could form a stable suspension in biological fluids with various p Hs and tonicity.The result of hemolysis activity revealed that PDC-M possesses low haemolytic toxicity,good hemocompatibility and good suitability for intravenous injection.The in vitro study on anti-tumor effect of PDC-M: Anti proliferative effect of PDC-M and DOX in HepG2 cells,MCF-7 cells and A549 cells was determined by MTT.According to the IC50 values,PDC-M against HepG2 cells were more effective than PDC-M against MCF-7 cells and A549 cells.The enhanced in vitro cytotoxicity of PDC-M against HepG2 cells may be attributed to galactose acid of pectin that can combine with asialoglycoprotein receptor(ASGP-R)of mammalian hepatoma cells.To investigate the important role of galactose acid in the cellular uptake of PDC-M,a receptor competition assay by selecting galactose acid as the competitive reagent was conducted.Consistent with our hypothesis,when PDC-M and galactose were added to the wells simultaneously,the fluorescence intensity of HepG2 cells significantly decreased.It suggested that the cellular uptake of galactosylated nanomedicine was mediated by the ASGP-R.The in vivo study on anti-tumor effect of PDC-M: The antitumor efficacy of PDC-M was studied in athymic BALB/c nude mice bearing HepG2 cell xenografts.Antitumor activity was evaluated in terms of tumor volume,body weight,tumor growth and terminal tumor weight.Compared to DOX,PDC-M had higher in vivo safety and therapeutic activity in animal models.Conclusion: The PDC-M exhibited higher antitumor efficacy and lower toxicity,implying that PDC-M is a highly promising drug delivery system for hepatocellular carcinoma treatment.