Regulating Surface Characteristics Of Nanomaterials For Cancer Radiosensitization

Radiation therapy?RT?is widely used for anti-cancer in clinic.However,there are still some bottleneck problems limiting the effect of RT.For one thing,the low efficiency of water radiolysis results in insufficient yield of hydroxyl radicals?·OH?,which play important roles in inducing serious damage to cancer cells.For another,cancer cells usually devote themselves to repairing the damage caused by RT for surviving.Fortunately,the developing nanotechnology brings more chances for solving the problems in RT.For example,the surface characteristics of nanomaterials are abundant and easy to control.Through introducing appropriate superfacial properties,nanomaterials will increase the reactivity of H₂O.Meanwhile,nanosized interface has potential to interfere certain biological process,leading to reduced radioresistance of cancer cells.Hence,for solving the bottleneck problems of RT,in this dissertation,the author will reflect on the relationship between surface characteristics of nanomaterials and radiosensitization,then synthesize various nanoparticles with unique surface properties,and finally systematically study their applications in RT.The major results are showed as follows:1.The application of Pt?IV?ligand in X-ray-induced photodynamic therapy:through combining high depth of penetration of RT and well yield of·OH of photodynamic therapy?PDT?,X-ray-induced PDT?X-PDT?has considerable potential for applications in cancer therapy.However,the low efficiency of converting X-rays to fluorescence presents a challenge for the use of X-PDT.In this study,a new method based on LiLuF₄:Ce@Si O₂@Ag₃PO₄@Pt?IV?nanoparticles?LAPNP?is presented that could be used to enhance the curative effect of X-PDT.To make full use of the fluorescence produced by nanoscintillators?LiLuF₄:Ce?,a cisplatin prodrug Pt?IV?was utilized as a sacrificial electron acceptor to increase the yield of·OH by increasing the separation of electrons and holes in photosensitizers?Ag₃PO₄?.Additionally,cisplatin is produced upon the acceptance of electrons by Pt?IV?and further enhances the damage caused by·OH.Pt?IV?can also endow LAPNP with favourable solubility.Via the assistance of multifunctional Pt?IV?,the potential of LAPNP to enhance the effects of X-PDT has been demonstrated.This work will bring more ideas for enhancing the effect of X-PDT.2.Superficial defects of nanomaterials increase the reactivity of water for radiosensitization:the insufficient yield of radiolysis of water limit the curative effect of RT,due to the high stability of O-H bond of water molecules.In this study,the author presents the radiosensitization strategy of‘water activatation',in which superficial defects are used for enhancing the yield of·OH.The author synthesized two kinds of nanomaterials,Bi OCl nanocrystals containing abundant Bi vacancies?Bv NCs?and Ti O₂ nanocrystals containing abundant Ti³⁺doping ions(¹²⁵I-Ti O₂).Bi vacancies are introduced via increasing the reaction temperature,while Ti³⁺come from the reaction between Ti⁴⁺and ¹²⁵I-emitted auger electrons.These defects will firstly absorb H₂O molecules and stretch the O-H bonds to decrease the energy barriers of H₂O radiolysis.Then upon irradiation of X-rays,these H₂O molecules will more easily convert to·OH for enhanced curative effect.These findings confirm the potential of increasing the reactivity of water in radiosensitization,which will be as important as the strategy of high-Z atoms induced radiosensitization.3.Nanosized surfaces interfere with the synthesis of protein for radiosensitization:cancer cells have ability to repair RT-induced damage.In this study the author synthesized mesoporous silica nanoparticles containing high concentration of H₂O₂?MSHNs?to solve this problem.MSHNs can concentrate and immobilize H₂O₂on their surface via hydrogen-bond interaction and nano-confinement effect.These interfaces with abundant H₂O₂ can make serious damage to ribosomes.As a result,these cancer cells cannot express corresponding repair proteins to resist the damage of RT,leading to enhanced effect of RT.These findings indicate that interfering with the production of protein has potential to reduce the radiation resistance of cancer cells.This strategy of‘interfering with the synthesis of protein'will bring more chances and ideas for radiosensitization.