Preparation And Application Of Nanomicelles For Radiotherapy Of Tumors

Breast cancer is one of the highest incidence of cancer in women.Its treatment plan is based on radiotherapy combined with surgical treatment.However,due to the dose limitation of radiotherapy itself and the resistance of some tumor cells to radiotherapy,the role of traditional radiotherapy is limited.Therefore,in order to improve the effectiveness of radiotherapy and reduce its toxic and side effects,it is necessary to develop new alternative treatments,such as the combination of radiotherapy and chemotherapy,the application of radiotherapy sensitizer.The radiation dose is reduced while increasing the sensitivity of the tumor tissue to radiotherapy.With the rapid development of nanotechnology and nanomedicines,nanomaterials have attracted widespread attention in improving the efficacy of radiotherapy and overcoming radiotherapy resistance of tumor tissue.The nanomicelles can not only directly carry radioactive isotopes to the tumor tissues to exert internal radiotherapy effects,but also serve as sensitizers for radiation therapy with radiosensitizing effects of heavy elements or chemotherapeutic carriers.Based on the above two different application methods of radiotherapy,a novel radiotherapy sensitizer and radioisotope carrier were designed.The effectiveness of the related system was evaluated using human and mouse-derived breast cancer cells as research subjects.In the first part,we synthesized the block polymer PEG-PTIBA by the macromolecular chain transfer agent PEG-CTA.Through the introduction of disulfide bonds,the polymer micelles have the properties of reduction and drug release.The synthesis of prodrug PTX-TIBA modified by triiodobenzoic acid(TIBA)resulted in high drug loading,good dispersibility and long-term stability.Since PTX itself has a sensitization effect of radiotherapy,modification of triiodobenzoic acid on the polymer chain and on PTX is expected to further increase the X-ray absorptive capacity and thus improve the radiotherapy effect.The results of cytotoxicity test showed that the drug-carrying system has the ability of inhibiting the proliferation of tumor cells and can be used as a chemotherapy aid to radiotherapy;cell cycle experiments prove that the drug-loading system can arrest cells in the G2/M phase and is important for improving the radiosensitivity of cells.significance.In the second part,a block polymer containing tyrosine methyl ester functional group and N-2-hydroxypropyl methacrylamide(HPMA)was synthesized by small molecular chain transfer agent CTA.The tyrosine group on the segment can be Radioactive 131I was introduced by a substitution reaction for endogenous radiotherapy.In this study,the biodistribution of micelles in animals was investigated.The results of in vivo experiments showed that polymer micelles with longer hydrophilic segments have a longer blood circulation time and have a better ability to concentrate in tumor sites.Ideal radioisotope carrier.