Preparation,Performance Regulation And Application Of Neodymium-sensitized Rare Earth Fluoride Optical Diagnostic And Therapeutic Nanoprobe

Cancer has seriously damaged human life and health.In order to find a way to diagnose and treat early tumors,researchers have invested a lot of energy in extensive research.In recent years,rare earth nanomaterials have been widely used in the fields of fluorescence microscopy imaging,deep tissue bioimaging,nanomedicine,optogenetics,and security labeling due to their unique luminescence characteristics and excellent magnetic properties.Rare earth nanomaterials could be excited by near-infrared（NIR）light to produce up-conversion luminescence for up-conversion fluorescence imaging,and down-conversion luminescence used in second near-infrared（NIR-II）biological imaging,which made important progress in the field of biomedical imaging,especially in the field of tumor detection and treatment.Rare earth fluorides,as excellent up-conversion luminescent hosts,were widely used in optical imaging.Most of the Yb³⁺/Er³⁺co-doped rare earth fluorides were mainly activated by 980 nm laser to produce up-conversion emission,which would lead to the overheating effect of biological tissues,and then lead to biological tissue damage and cell death.Therefore,there is an urgent need to develop new rare earth upconverting nanoparticles（UCNPs）excited by808 nm laser.In addition,rare earth UCNPs have important application prospects in photodynamic therapy（PDT）as a new generation of optical converters.However,the traditional rare earth UCNPs were mainly loaded with a single photosensitizer,which greatly limited the utilization efficiency of up-conversion multicolor luminescence.Based on this,in this thesis,we design the Nd³⁺-sensitized rare earth fluoride-based dual photosensitizer optical diagnosis and treatment nanoprobe for collaborative treatment,laying the foundation for the construction of a new diagnosis and treatment platform integrating multimodal imaging diagnosis and treatment.The main results obtained are as follows:（1）The high-temperature co-precipitation method was used to prepare Nd³⁺-sensitized core-shell rare earth UCNP with uniform size and good dispersity,and the crystal phase,structure and optical properties were studied.The results showed that the sample emitted up-converted light at 550 nm,650 nm and NIR-II light at 1525 nm under the excitation of 808 nm laser.The 808/980 nm laser induced thermal effect on biological tissues was also evaluated.The results showed that the Nd³⁺-sensitized rare earth core-shell nanocrystals solved the problem of tissue overheating effect caused by the traditional 980 nm laser.（2）A hollow drug-loadable UCNP@mSiO₂@Mn O₂nano-energy-converter was constructed by coating mesoporous silica（mSiO₂）and in-situ depositing manganese dioxide（Mn O₂）via microemulsion method.And build the UCNP@mSiO₂@Mn O₂-RB/ZnPc nano-system integrated photo-diagnosis and treatment by further loading dual photosensitizers of Rose Bengal（RB）and zinc phthalocyanine（ZnPc）.Utilizing its up-conversion multicolor luminescence and fluorescence resonance energy transfer,the synergistic activation of dual photosensitizers was realized and the production of reactive oxygen species（ROS）was increased.Moreover,the hypoxia problem of the tumor microenvironment was further solved by using the Mn O₂-based catalytic reactions,leading to improve the efficacy of photodynamic therapy（PDT）.In addition,NIR-II imaging and tumor microenvironment responsive T₁-weighted magnetic resonance（MR）imaging were realized,which improved the accuracy of tumor diagnosis.These findings provide a new strategy for the design of nanoprobes for photo-diagnosis and treatment.（3）On the basis of Nd³⁺-sensitized core-shell UCNPs,we further constructed a nanoprobe with combination of photothermal and PDT by coating dopamine（PDA）and loading dual photosensitizers.This nanoprobe presented high photothermal conversion efficiency（30.9%）and excellent ROS generation,laying the foundation for the design of nanoprobe for photothermal/PDT synergistic treatment.