Construction Of Reactive Oxygen Species Responsive Nanomicelles And Evaluation Of Their Antitumor Activity

Cancer is still a major disease that threatens human health.People are committed to find ways to solve the problems of cancer treatment.The polymer nanocarriers have good biocompatibility,long circulation time in the body,and can be targeted to enrich tumor tissues,which are increasingly becoming a good carrier for targeted tumor therapy.The use of the characteristics of the tumor microenvironment to design drug delivery systems is considered a key to achieve cancer-targeted therapy and can improve the efficacy of chemotherapy.This feature involves many aspects,of which oxidative stress from reactive oxygen species(ROS)such as H2O2 is of increasing concern.In this work,a novel ROS-responsive nanocarrier for antitumor drug delivery was designed.Polyaspartic acid-grafted responsive side chain phenylboronic acid serine(BSer)was used as a macromolecular scaffold for solubility and biocompatibility.Doxorubicin(Dox)as a model drug.The change in BSer substitution was achieved by varying the feed ratio in the polysuccinimide(PSI)ring opening hydrolysis.The physicochemical properties of the micelles were measured by NMR,Malvern laser particle size analyzer,infrared spectrophotometer and electron microscope.The response of nanomicelles was examined by comparing the difference in the cumulative release rate of doxorubicin when different concentrations of H2O2 were added under different pH conditions.The results of MTT assay,flow cytometry,and confocal laser scanning microscopy(CLSM)showed that the vector had better cell selectivity.Compared to normal cells(L929),the effect of drugs on cancer cells(A549)is more pronounced.Finally,4T1 cells were used to construct a mouse model of breast cancer.The in vivo anti-tumor effect of drug-loaded micelles was further confirmed by comparing the tumor inhibition rate,tumor volume,organ distribution,and section staining of free drugs and carriers.A series of experimental results show that the active oxygen-responsive nanocarriers have better tumor targeting effect,open up new ideas for tumor-targeted therapy,and can subsequently be packaged with different drugs or micro RNA and other gene fragments,which has a broad application prospects.