Facile Preparation And Radiotherapy Application Of An Amphiphilic Block Copolymer Radiosensitizer

Radiotherapy has become one of the major methods of tumor therapy in recent years because of its significant effect.It is estimated that nearly 70%of cancer patients are willing to have a cancer treatment by accepting a dose of radiotherapy.At present,the key problem in the field of tumor radiotherapy is how to deal with the radiation resistance of hypoxic tumor cells.Considering high energy radiation can seriously affect the normal tissues while irradiating the tumor,even cause considerable damage to them,which makes it impossible to kill the hypoxic tumor cells by merely increasing the radiation dose continuously.It is reported that the use of appropriate radiotherapy sensitizer can not only improve the radiotherapy of malignant proliferation tumors effectively,but also significantly reduce the radiation dose required for radiotherapy,thus avoiding the possible damage to normal tissues.In this paper,we have studied a novel amphiphilic block polymer radiotherapy sensitizer.When compared with small molecule radiotherapy sensitizer,this kind of radiotherapy sensitizer not only possesses a higher sensitization enhancement ratio,but also has a more stable and efficient enrichment in the tumor site,which successfully help it improve the effect of radiotherapy significantly.This polymer radiotherapy sensitizer can be synthesized by simple and efficient chemical reactions,followed by self-assembly in water.In order to further learn the radiosensitization effect of polymer micelle,the radiotherapy sensitization at the cell level and the mouse tumor model level was evaluated respectively.The main contents and major conclusions of this study are presented as follows:1.Firstly the polymer micelle was synthesized and prepared.One carboxyl group of glutamic acid was reacted with propargyl alcohol to obtain alkynyl group-modified glutamic acid,which formed into PEG-b-PPLG through the ring-opening polymerization initialized by single-ended amino polyethylene glycol monomethyl ether.The hydroxyl group at the terminal end of metronidazole are transformed into azide group after a series of organic chemical reactions.Finally,click chemistry occurred so as to combine the two kinds of molecules together,and finally the monodisperse PEG-b-P(PLG-g-MN)was obtained.The degree of polymerization of the two blocks is confirmed to be 113 and 60,respectively.Dissolved in a small amount of acetonitrile and added into water,polymer micellar nanoparticle was formed by concentrating the organic solvent.The stable polymer micelle has a particle size of around 60 nm.2.In order to study the biocompatibility and radiotherapy sensitization properties of polymer micelle from the cellular level,the polymer micelles were directly applied to the cells and radiotherapy was performed with X-ray.The results showed that the polymer micelle did not produce any significant toxicity after being uptaken by the cells,and the survival rate of the hypoxic cells was sharply decreased after the X-ray irradiation treatment,which showed a significantly better radiosensition effect than small molecule radiotherapy sensitizer.3.Finally,the mouse tumor model was established to study the distribution of polymer micelle in vivo and the anti-tumor effect of radiotherapy.The results showed that the polymer micelle can not only accumulate in the tumor site within a short time but keep stably for a long time there.After radiotherapy,the polymer micelle exhibited outstanding anti-tumor effect and do not cause any damage to the normal organ tissues meanwhile.