Polymer-based Nanocomposites For Radiosensitization And Radiation Protection

High-energy ionizing radiation can cause cellular damage by leading to ionization of molecules and generating of highly toxic free radicals.On the one hand,this allows ionizing radiation to effectively destroy tumors,thus brings radiotherapy（RT）,the most basic and effective cancer treatment method.On the other hand,radiotherapy and all kinds of artificial and natural ionizing radiation can cause serious damage to healthy tissues and organs.So researchers are focusing on enhancing the therapeutic effect of RT and avoiding the harm of ionizing radiation to human health.In recent years,polymer-based nanocomposites have attracted attention due to their good biocompatibility and excellent biological functions,providing new possibilities for the realization of radiosensitization and radioprotection.According to the application requirements,researchers can select appropriate structural units,control exactly the synthesis steps and obtain nanomaterials with specific composition,structure and function which could be effective radiosensitizers or radioprotective agents.In the second chapter,we designed and synthesized Tween-20-modified BiVO₄/Bi₂S₃ heterojunction nanorods（HNRs）integrated two imaging functions of X-ray computed tomography（CT）and photoacoustic（PA）and three cancer treatments functions of radiotherapy（RT）,radiocatalytic therapy（RCT）and photothermal therapy（PTT）.Due to the high X-ray absorption coefficient of Bi and the strong near-infrared absorption of Bi₂S₃,BiVO₄/Bi₂S₃ HNRs can be used as efficient CT/PA dual-mode imaging contrast agents,radiosensitizers and photothermal agents.More importantly,there is a Type-II energy level structure between BiVO₄ and Bi₂S₃,which is beneficial to promote the separation of X-ray excited electron-hole pairs,thereby realizing efficient radiocatalytic reaction,leading to more free radical production for better therapeutic effect.PTT can not only effectively ablate tumors,but also further enhance the therapeutic effect of RT and RCT.The results of in vitro and in vivo cancer treatment experiments confirmed that our BiVO₄/Bi₂S₃ HNRs have no obvious toxicity,and this RT/RCT/PTT synergistic treatment regimen has a higher therapeutic effect than monotherapy.In the third chapter,we designed and synthesized glucose oxidase（GOx）and polyethylene glycol-folate（PEG-FA）modified Bi OI/Bi₂S₃@polydopamine（PDA）heterojunction nanosheets（NSs）,which integrate two imaging functions of CT/PA and three cancer treatment functions of RT,RCT and starvation therapy（ST）.The strong X-ray absorption of Bi and I and the strong near-infrared absorption of Bi₂S₃ and PDA make Bi OI/Bi₂S₃ NSs can be used as effective CT/PA dual-mode imaging contrast agents.The Bi OI/Bi₂S₃ heterojunction not only effectively inhibits the recombination of electron-hole pairs generated by X-ray excitation,but its unique Z-scheme energy level structure can also maintain the high redox ability of electrons and holes,so that they all can participate in the formation of·OH,thereby enhancing the RCT therapeutic effect.In addition,the modification of GOx can not only consume glucose and cut off the energy supply of cancer cells to inhibit tumors growth,but also provide sufficient H₂O₂ for RCT to generate more·OH,achieving better therapeutic effect.Benefiting from the cascading and synergistic effects between RCT and ST,the NSs exhibited higher tumor therapeutic efficacy than monotherapy.In the fourth chapter,we designed and synthesized quercetin supramolecular polymers nanoribbons.Quercetin molecules assemble to form nanoribbons through non-covalent interactions such asπ-πinteractions and hydrogen bonds.The quercetin nanoribbons still maintain the strong free radical elimination ability of quercetin,and can withstand the harsh p H value of the digestive system.Not only that,the dispersibility of quercetin nanoribbons in water is significantly improved,which is beneficial for their function in the water-rich mucosal layer of the intestinal.Therefore,the quercetin nanoribbons can be used for intestinal radioprotection agents by simple orally injected.The in vitro and in vivo experimental results show that the quercetin nanoribbons can effectively eliminate free radical generated by X-ray,reduce the damage of DNA and mitochondria,protect the proliferation ability of intestinal cells and avoid the occurrence of apoptosis.Thereby it can maintain the structure of villi and crypt of intestinal and inhibit weight loss and death caused by X-ray.