Multilayer Core-shell Nano-composite For NIR-triggered Enhanced Photo Combination Therapy

Cancer is one of the most lethal disease in the world.In recent years,photothermal therapy（PTT）has attracted much attention due to its unique advantages,such as high efficiency,minimal invasiveness,and low toxic side effects.Due to the unique growth mechanism of malignant tumor cells,the concentration gradient during tumor formation makes it difficult for reagents to enter,which means that the use of PTT alone is not enough to completely kill cancer cells,combined therapy that based on all-in-one nanomaterials can make up for PTT’s deficiencies.In addition,the excessive heat generated by PTT often damages normal cells.It is necessary to develop imaging functions to track and discriminate PTT in order to achieve accurate diagnosis and treatment.Rare earth up-conversion nanophosphor（UCNP）have a series of advantages in biological imaging applications because of their unique luminescence mechanism.Combining the rare earth UCNPs with photothermal reagents for tumor’s temperature detection before and during phototherapy can reduce the side effects while improving the accuracy of PTT treatment.This thesis mainly focuses on the development of multilayer core-shell structure composite nanomaterials.The main contents are list as follow.（1）In view of the limitations of the cancer treatment effect of PTT alone,we took the photothermal material Au NR as the core,by covering zinc oxide nanoshell to produce reactive oxygen species（ROS）to damage the DNA of cancer cells.Then the cancer treatment drug doxorubicin（DOX）was loaded into the mesopores through electrostatic adsorption,where mesoporous silica improved the biocompatibility and drug loading effect.Controlable near-infrared（NIR）-triggered DOX-released nanocomposites DOX-Au NR@Zn O@Si O₂was successfully prepared.The nano-composites have a novel structure,uniform particle size,good dispersion and great biocompatibility.Optical measurements have verified that DOX-Au NR@Zn O@Si O₂exhibits high photothermal conversion efficiency（η=20.85%）under illumination by 808 nm light to offer hyperthermia tumor ablation.The drug release experiment results demonstrate that the thermal expansion triggered by NIR light can quickly promote the release of the drug DOX.The treatment results of He La tumor cells prove that the combined treatment of chemotherapy,hyperthermia and ROS treatment can lead to more than 99%of cell apoptosis.This work provides a guide for the development of other highly efficient“all-in-one”multifunctional theranostic platform.（2）In order to overcome the limitation of excessive heat caused by the photothermal conversion effect of photothermal reagents,we designed and synthesized a rare earth upconversion luminescent nanomaterial.The nano-core was prepared by the solvothermal method,and the multi-layer core-shellstructurewasobtainedbytheepitaxialgrowthmethod.Na YF₄:Yb,Er@Na Yb F₄@Na Nd F₄:Yb nanoparticles are supposed strong upconversion luminescence（UCL）irradiated with 808 nm NIR light.Firstly,the sensitizer Nd³⁺in the absorption layer is excited by 808 nm NIR light,then the energy is transfered from Nd³⁺to Yb³⁺in the same layer through ion cross relaxation.Then,the energy is further transfered to the the activation laye by energy migration of Yb³⁺in the enery relay layer through inter-lattice diffusion.At last,the activator Er³⁺in the inner core captures the migration energy to generate a strong upconversion emission.Among them,the active layer,the energy relay layer and the absorption layer are Na YF₄:Yb,Er,Na Yb F₄and Na Nd F₄:Yb.We effectively enhanced UCL by growing Na YF₄inert protective layer and adjusting the thickness of the Na Yb F₄energy relay layer.The experimental results demonstrate that the composite structure of Na YF₄:Yb,Er@Na Yb F₄@Na Nd F₄:Yb@Na Yb F₄is successfully prepared,and the thickness of the energy relay layer is effectively adjusted.This provides the possibility of using NIR up-conversion luminescence imaging to detect the intrinsic temperature of photothermal reagents.