The Optimization Of Dosage Form Of Anti-tumor Peptide M1-21

FOXM1(Forkhead box M1)is one of the members of the FOX transcription factor family.A large number of studies have shown that FOXM1 is overexpressed in various tumors and play a vital role in the occurrence and development of tumors,which is usually related to the adverse effects of tumor patients.Therefore,FOXM1 has been used as the target of anti-cancer drug development very early,and a series of FOXM1 small molecule inhibitors have been developed for the treatment of tumors.Beside of this,some peptides originated from FOXM1 can effectively kill tumor cells,which provides a new idea for the development of anti-tumor medicines.In recent years,peptide drugs developed rapidly as a type of innovative drugs,used to treat various human diseases including cancers,and always achieved good outcome.Peptides have their own advantages such as strong target binding and high safety.But it also has drawbacks,such as instability,short plasma half-life,and poor cell permeability.Although the development of peptide drugs has made some progresses,it still faces great challenges.Therefore,how to overcome the defects of the polypeptide becomes the key to whether some pharmacologically effective polypeptides can be made into medicine.At the same time,polypeptides can self-assemble into various nanostructures,so they are very suitable for introducing nano-drug delivery systems,making polypeptides into nano-dosage forms,and using the advantages of nano-delivery systems to improve the anti-tumor effect of anti-tumor polypeptides.In this paper,peptide M1-21 is a peptide with anti-tumor activity screened out by the laboratory.The introduction of TAT is used to mediate the entry of polypeptide M1-21 into cells and the introduction of D-type amino acids increases its stability.The antitumor peptide M1-21 monomer was used to create nanoparticles(Nano-M1-21,about50 nm)by the method of desolution.The characteristics of Nano-M1-21 were determined by the dynamic optical dispersion(DLS)and the low pressure transmission electron microscopy(TEM).The stability of Nano-M1-21 particles was measured at 37 degrees centigrade in vitro.To verify the anti-tumor effects of Nano-M1-21,we used breast cancer MDA-MB-231,MCF-7 and 4T1 cells to show that Nano-M1-21 was easily absorbed by the cells and its tumor inhibitory concentration was lower than that of monomer peptide.In the MMTV-Pymt mice,Nano-M1-21 is found to be enriched in the tumor site through the EPR effect.With a mouse breast cancer 4T1 cell-grafting tumor model,we found that Nano-M1-21 showed a good suppressive effect to the tumors.In conclusion,compared to the monomer peptide M1-21,the optimized Nano-M1-21 nanoparticles provide benefits to improve the cellular uptake and anti-tumor effects.