Resveratrol-based Polymer Microsphere For Ionizing Radiation Protection

Radioisotopes and radiation technology is developing rapidly,ionizing radiation is widely used in various fileds such as industry and medicine.However,high-energy radiation can also cause significant damages in healthy tissues via damaging DNA and producing reactive oxygen species（ROS）and induce cancer,physical deformity even death.However,the existing radioprotective agent has serious side effects,high toxicity and short half-life.There is no practical radioprotective agent for routine clinical application.Therefore,it is urgent to design highly effective radioprotectants with low toxicities that can satisfy the increasing demands of cancer radiation therapy.In recent years,nanocarriers have provided opportunities to overcome the shortcomings of low solubility,side effects and lack of stability.Currently,many nanocarrier-based drug delivery systems for radiation protection have been reported which encompass organic polymer nanocarriers,inorganic nanocarriers,as well as nanosize radioprotectors assembled by molecular radioprotective drugs.Resveratrol,a polyphenolic compound primarily found in grapes,nuts,fruits,and red wine.Its pharmacological effects have been reported to include antioxidant,anti-inflammatory,anticancer.Resveratrol has been confirmed to have free radical scavenging effects that protect normal tissue cells from radiation-induced damage.However,resveratrol presenting some disadvantages such as low chemical stability,hydrophobicity,low bioavailability and a high metabolization rate in vivo which limits its biological application severely.In this context,we designed and prepared resveratrol-based polymer microsphere with free radical scavenging activity as radioprotectants and explored their application in the filed of ionizing radiation protection.In chapter 2,we prepared resveratrol-based polymer microsphere by two methods.By comparing the two preparation methods,we chose the method to prepare polymer microsphere by condensation of resveratrol and amino acid by Mannich,and the physicochemical properties of the polymer microsphere were characterized in detail to investigate the potential as radioprotective agent.Resveratrol molecules assemble to form polymer microsphere through non-covalent interactions such asπ-πinteractions assemblies.The average diameter of the polymer microsphere is 138 nm,which has good stability and can effectively scavenging DPPH and ABTS free radicals.The polymer microsphere has low cytotoxicity and could be efficiently taken up by HUVEC cells.In chapter 3,we researched the radiation protection ability of polymer microsphere by in vitro experiments.We tested the cytotoxicity,intracellular ROS level,DNA damage,mitochondrial membrane potential,GSH level,cytochrome C,Caspase-3,BAX,BCL₂ protein expression before and after X-ray irradiation,and the experimental results showed that the nanomaterials had excellent radiation protection ability.The in vivo experimental results show that the polymer microsphere has good biocompatibility and can be used as free radical scavenger to effectively get rid of the ROS free radicals generated by X-ray,improve the level of superoxide dismutase SOD and reduce the level of ROS harmful by-product MDA,decrease the radiation-induced DNA damages,recover the radiation-decreased BMNC,protect the proliferation ability of cells,maintain the normal structure of intestinal tissue and improve the overall survival rate of irradiated mice.In summary,it was found that the resveratrol-based polymer microsphere showed excellent radiation protection ability in both in vivo and in vitro experiments and is a potential radioprotectant.