Preparation Of Peg Hydrogel Microspheres Drug Carriers And Their Use For Drug Synergy And Targeted Therapy In Breast Cancer

Chemotherapy is a very common modality in the treatment of breast cancer.However,due to the low selectivity of drugs in chemotherapy,which can cause uncontrolled damage,the development of drug carriers with targeting-mediated effects on cancer cells has been a very important research direction.The exploration of ideal drug carriers with excellent biocompatibility,high in vivo stability,therapeutic efficacy and targeting effect on cancer cells is importance throughout cancer treatment.In this paper,peptide Nanofibers(PNFs)were designed with different functional amino acid sequences in peptide chain segments,and loaded with adriamycin(DOX)in combination with metformin drug carbon dots(CDs)and degradable eightarm polyethylene glycol(8-PEG)hydrogel microspheres.Building a combination drug delivery system for breast cancer treatmentd with both cellular targeting and synergistic therap.The details are as follows:(1)Preparation of hydrogel microspheres that can be used for drugcarrying degradation without harm to cells.The 8-PEG hydrogel microspheres were obtained by a simple emulsion polymerization method with ammonia water as crosslinking agent and Michael additive reaction with monomer.The microspheres have a uniform spherical shape as well as an internal network structure.After Image J software,the average size of the microspheres is 6.66μm.In addition,the effects of different monomer ratio,emulsifier quality ratio,cross-linking agent content and mechanical stirring speed on microspheres were investigated.It was found,8-PEG the proportion of PEG was inversely proportional to the size of the microsphere,and the content of the crosslinking agent and the stirring speed were proportional to the size of the microsphere.The prepared hydrogel microspheres have good swelling properties and stability.Good degradation performance at p H=6.6,p H=7.4,and p H=8.The cytotoxicity experiment shows that it has good biocompatibility and low cytotoxicity,and has the condition as a drug carrier.(2)Preparation and study of targeted treatment of breast cancer and synergistic drug carrier system.Multifunctional PNFs are prepared from RGD-AEAKAEAK-YWYAF-CCY-RGD polypeptide sequences.With π-πconjugate connecting metformin drug carbon point,through thiol and 8-PEG later PEG)hydrogel microspheres double bond "click" reaction.Loading DOX as a killer for breast cancer cells,the drug load rate is 90%.In drug release experiments,the maximum releases under p H=6.6 and p H=7.4 were 38.8%and 27% respectively.With MDA-MB-231 as experimental cells,it is proved that the drug carrier and functional component have good biocompatibility to cells.Cell survival is basically above 80%.Based on the drug concentration,a concentration gradient experiment was performed to test cell cytotoxicity.It was proved that PEG/PNFs-CDs had the best effect on the treatment of cancer cells when they were used as drug carriers.The effect of PEG/PNFs as a carrier is much lower than that of PEG/PNFs-CDs,which proves that the therapeutic effect is greatly enhanced due to the synergistic effect of carbon dots and DOX.The targeting effect of the drug carrier was tested by an inverted fluorescence microscope.The polypeptide nanowires containing and without RGD were used with Cy5.5 as the imaging factor.By comparing the endocytosis effect of the microspheres carrier in the cell,the targeting effect of the carrier was proved.It can achieve better therapeutic effect and has a good application prospect.