Preparation And Performance Evaluation Of Tumor Microenvironment Responsive Polymer Nano Drug Carrier

The differences in tumor microenvironment,normal organs and tissues make the tumor microenvironment responsive polymer nanodrug carriers receive widespread attention.Using its characteristics,targeted drug delivery and controlled release of anticancer drugs can be achieved,and the therapeutic effect is significantly improved.Based on the characteristics of tumor microenvironment,in this paper,three new types of tumor microenvironment responsive polymeric nanodrug carriers were designed and synthesized respectively by RAFT polymerization,and their structures and properties were studied.The research contents are as follows:(1)A series of PEG-b-P(DPA-co-CPTssMA)(PEDC)polymeric prodrugs were synthesized by one-step RAFT polymerization using DPA and CPTssMA as comonomers.The structure of monomers and polymeric prodrugs was verified by]H-NMR and GPC tests.DLS and TEM tests showed that the polymeric prodrugs can self-assemble into spherical nanoparticles(NPs)in aqueous solution and the particle size increased as the length of the PCPTssMA segment increased.In vitro drug release showed that in acidic containing 10 mM DTT environment,the CPT release rate was fast and the amount of cumulative release was larger,while in the physiological environment,only a small amount of CPT was released,thus showing a controlled release property.Through the CLSM,it was observed that prodrug NPs can rapidly and efficiently carry CPT to the cytoplasm by endocytosis and rapidly release CPT.MTT assay showed that polymeric prodrugs have a strong ability to inhibit cell proliferation.(2)Using MAIpGP and PDEMA as monomers,PMAIgGP-b-PPDEMA(PMgPP)amphiphilic block polymers were synthesized via two-step RAFT polymerization and one-step deprotection reaction.The structure of monomers and polymers was verified by 1H-NMR,UV-Vis and GPC tests.Taking DOX as the model drug,UV-Vis was used to study the drug loading of PMgPP CC NPs,and found that the drug loading was up to 13.4%,presenting a good load capacity.In vitro drug release showed that the release rate of DOX was faster and the amout of cumulative release was higher in 10 mM GSH solution,with a cumulative release amount of 50.6%at 46 h,thus showing a controlled release property.Through CLSM,it was observed that PMgPP/DOX CC NPs can quickly and efficiently carry DOX to the cytoplasm by endocytosis and quickly release DOX in the cells.MTT assay showed that the polymer had good biocompatibility and PMgPP/DOX CC NPs showed a strong inhibitory activity on HepG2 cells.(3)FA-PMAIgGP-b-P(DPA-co-PDEMA)(FA-PMgDP)amphiphilic block copolymers were synthesized by two-step RAFT polymerization and one-step deprotection using DPA and PDEMA as the comonomers.The structure of polymers was verified by 1H-NMR,GPC and UV-Vis tests.Using DOX as a model drug,UV-Vis study showed that FA-PMgDP exhibited a good loading capacity for DOX with drug loading as high as 15.8%.FA-PMgDP/DOX CC NPs were stable in physiological environment and had a low cumulative drug release.However,the rapid release was achieved in acidic containing 10 mM DTT environment,and the cumulative release amount can up to 98%at 47 h.Through CLSM and flow cytometry,it was observed that the FA-PMgDP/DOX CC NPs had effective ability to enter the cell and controllable release properties.MTT assay showed that the polymer has good biocompatibility and FA-PMgDP/DOX CC NPs showed a strong proliferation inhibitory activity on HepG2 cells.