Studies On Design,Synthesis And Activity Of Targeted-Cell Penetrating Peptides

Drug delivery system refers to the space,time and dose of drug distribution in the body.Now there has a lot of different drugs in the international market,especially anti-tumor drugs,which need to cross the cell membrane into the nucleus where it will play a role in the cancer treatment.Very common problem of the anti-tumor drugs is their low efficiency in transmembrane and low-drug targeting between cancer and normal tissue,which will cause some side effects,limiting drugs application.Cell-penetrating peptides(CPPs),consisting of several to forty amino acids,can enter the cell through the cell membrane.Since its discovery,when the concept been proposed initially,the CPPs receive more and more attention for its low toxicity and high efficient in transmembrane properties.In the family of CPPs,the cyclic cell penetrating peptides(cCPPs)shows better transmembrane characteristic.Cell-targeted peptides,using the differences between targeted cells and non-targeted cells,such as cell receptor expression type,pH and other characters,can selectively targeted to the specific parts of the body,which is definitely contribute to the drug treatment.In this study,we connect the cCPPs and cell targeting peptide to improve the drug carrier's targeting and transmembran capability,reducing drug's toxicity to the normal cells.Cell uptake experiments(at a concentration of 5?mol/L,2h),the results show that peptide-carriers can carry more fluorescent(FITC)substances into the cells.Under the same conditions,laser confocal experiments show that amide ring cTAT and cR9 analogs can not only enter the cells in the DU-145,U251 and PC-3 tumor cell lines,but also clearly be seen their distribution in the nucleus,which does really has a sharp contrast to the free-FITC that adhere to the surface of the cell membrane.In the laser confocal experiments,we also can observed cell morphology is changing significantly,which is seen as the beginning of cell death.Cell cytotoxicity experiment(at a concentration of 50?mol/L,25?mol/L and 12.5?mol/L,2h)results shows that the peptide carriers alone have a low killing effect on the non-tumor HEK-293 A cells,and the survival rate of the cells was higher than 80% to 60% of cancer cell U251.In summary,the vector can carry more fluorescence into the cells and more importantly,they mainly distribute in the nucleus,which change the cell membrane's morphology and may promote the death of tumor cells.In addition,the peptide-carriers is linked to the anti-tumor drug Doxorubicin with hydrazone bond,to further improve the carriers the application.