Hyperbranched Polyphosphoester Micellar Nanomedicine For NIR Imaging Guided Thermo-chemotherapy To Reverse Acquired Resistance Of Breast Cancer Cells

Objective : To study hyperbranched polyphosphate nanomedicine for NIR imaging guided chemo-photothermal to overcome acquired multidrug resistance of breast cancer cells.Methods: 1.Construct the PEGylated hyperbranched polyphosphate nanomedicines(NP / DOX,NP / IR-780 and NP @ DOX + 780)containing DOX and / or IR-780.The stability of the delivery system in different media was studied.And characterization of drug-loaded nanoparticles,such as size,zeta potential,release behavior in the medium and photothermal curve.2.Using the multidrug-resistant tumor cells MCF-7 / ADR and MCF-7 as models,constructed the nanoparticles based on PEGylated hyperbranched polyphosphate containing DOX and / or IR-780(NP / DOX,NP / IR-780 and NP @ DOX + 780)to study the behaviors and effect of reversing breast cancer multidrug resistance in tumor cells.The concentration of DOX in the nanoparticles was measured by fluorescence spectrophotometer.By flow cytometry and laser scanning confocal microscopy measuring cell uptake,and MTT assay was used to demonstrate its inhibitory effect on cells.3.Animal model was constructed with multidrug-resistant tumor cells MCF-7 / ADR.The organ distribution and tumor accumulation of nanopharmaceuticals were monitored by a Xenogen IVIS Lumina system.To study the therapeutic effect of chemo-photothermal with the way of drug resistant tumor suppression study.Results : 1.We succesfully design and synthesize the hyperbranched polymer containing phosphoester bond and PEG,which can self-assemble into core-shell nanoparticles.This design strategy implements to overcome tumor drug resistance effectively and shows great potential for improved therapeutic therapy of cancer.2.In the cell experiments,by flow cytometry and laser scanning confocal microscopy measuring cell uptake,proving the nanoparticles could enter the cells through endocytosis and release the drugs in the cells,and could prevent the effect of P-gp on the expression of MCF-7 in MCF-7 cells.Compared with free DOX,NP / DOX could significantly increase the killing effect on cells and effectively overcome the drug resistance of tumor cells by MTT assay.3.Animal experiments have shown that the combination of photothermal therapy and chemotherapeutic therapy has a higher efficacy and can reverse the resistance in drug-resistant cell tumor models.Conclusion: PEGylated hyperbranched polyphosphates have been successfully synthesized.Combined chemotherapy and photothermal therapy are used to reverse the resistance in cancer.The EPR effect has a longer cycle time and enrichment in tumor tissue,and provides a great potential for cancer treatment strategies to overcome drug resistance.