| Cancer is one of the most devastating diseases in all over the world.In addition to the traditional surgical treatment of surgery and radiotherapy,chemotherapy is also a popular treatment method for cancer.However,there are many shortcomings with small molecule anticancer drug,for example,easy destroyment in body,short half-life,very serious side effects,often lead to less expected therapeutic effect and cause a secondary damage to patient.Therefore,how to safely and effectively transport small molecule anticancer drugs into body has aroused many researchers’ s interest in recent years.Polymer micelles can not only increase the solubility of anticancer drugs,prolong the half-life of drugs in the blood circulation,but also reduce the immunogenicity of drugs,improve the distribution of drugs in vivo,so as to improve the therapeutic effect.However,the polymer micelles also face some challenges:(i)the polymer micelles are dissociated or aggregated due to dilution or interaction with proteins in the blood after injection,leading to the result that the drug is released before reaching the tumor site and the treatment effect is reduced;(ii)the drug release of polymer micelles in the cell is not complete,and the drug concentration is too low to achieve therapeutic effect.Therefore,how to maintain stable in the cell and release the loading drug quickly and effectively become a hot topics in the study of drug carrier.Make use of the difference in pH and redox potential existing in human body,we designed and synthesized the pH and redox dual responsive drug carrier,which was self-assembled from the amphiphilic polymer poly(2-ethyl-2-oxazoline)-block-polyester with a disulphide bond.On the one hand,the pH responsibility come from the hydrophilic shell of micelle,which is beneficial for the micelle to escape from the endosome.On the other hand,the disulfide bond in the backbone of polymler can introduce redox responsibility to micelle,which can be cleaved by glutathione(GSH)in cell and the loading anticancer drugs is delivered fastly.In chapter 1,a introduction about the classification of nano-drug carrier,the preparation of polymer micelles and the development of environment responsive micelles was presented.In chapter 2,the cell experiments and animal experiments on the micelle of polymer poly(2-ethyl 2-oxazoline)-SS-poly-trimethylene carbonate(PEtOz-SS-PTMC)was performed.In vivo experimental results showed that PEtOz-SS-PTMC micelles could effectively inhibit the growth of tumor in mice.It further demonstrates that pH and redox dual-responsive PEtOz-SS-PTMC micelles have great potential for cancer treatment.In chapter 3,a novel amphiphilic polymer of poly(2-ethyl-2-oxazoline)-SS-polylactide(PEtOz-SS-PLA)with disulfide bond in the backbone was synthesized and the drug-releasing behavior of drug-loaded micelles was studied in C6 cells.The critical micelle concentration(CMC)of PEtOz-SS-PLA micelles is about 9 mg/L,indicating the good micellar stability of micelle.The in vitro release assay demonstrated that PEtOz-SS-PLA micelles could release the loading drug rapidly in the intracellular environment and inhibit the growth of cancer cells(C6).Laser confocal microscopy(CLSM)results showed that the loaded drug can enter the nucleus after 6 h incubation.Therefore,this biodegradable,dual responsive PEtOz-SS-PLA micelles have potential for cancer therapy.In chapter 4,the paper summarized the work of the paper,and put forward the future work. |
