The Application Of Polymer Modified Multifunctional Nanoprobes In Medical Imaging And Cancer Therapy

Nanomaterials have unique advantages in the field of biomedical applications,such as controllable synthesis,easy surface modification,long circulation time and loading multifunctional materials,therefore,nanomaterials have been widely used in imaging,clinical diagnosis and treatment.In this paper,facing the great demand of early diagnosis of malignant tumors and starting from the angle of the diagnosis and treatment of tumors,two kinds of multifunctional nanoprobes were designed and explored its application in T1/T2-MR/CT multi-modal imaging and photothermal therapy.The research follows two parts:1.We prepared bovine serum albumin（BSA）nanoparticles encapsulatedGd and Dy ions,and coated a polydopamine（PDA）on the surface through situ polymerization.Then,FA was modified to the surface of the particles by chemical bond,and the tumor targeted probe BSA:Gd,Dy@PDA-FA was successfully obtained.The probe is designed based on the following: rare earth element Gd is paramagnetic,and the Dy has strong X-ray absorption ability,which can be used as the matrix of MRI and CT imaging probes.The polydopamine has strong absorption in NIR region,and can convert light energyinto heat under NIR laserirradiation.Folic acid receptors are expressed on the surface of the tumor,so the high affinity of folic acid receptors with folic acid can be used to target tumor.The obtained BSA:Gd,Dy@PDA-FA probe had excellent stability and low toxicity.The temperature of the solution can be rapidly increased to 60°Cunder NIR laser irradiation.The cell survival rate was 8%after laser irradiation for 5 min confirmed that BSA:Gd,Dy@PDA-FA probes hadexcellent therapeutic effect.The probe had a high r1（9.47 mM-1 s-1）,r2（18.42 mM-1 s-1）and HU values（51.8 HU g-1）,which can be used for T1/T2-MR/CT multi-modality imaging.2.The rare earth fluoride nanoparticles are usually used as the carrier materials for multi-modal imaging probes due to their excellent light stability,low toxicity,controllable particle size and morphology.We prepared ultra-small and size tunable Dy doped NaGdF₄ nanoparticles through thermal decomposition method,and modified with PVP through ligand exchange,getting watersolubleT1/T2-MR/CT multi-modality imaging probes PVP-NaGdF₄:Dy.The systematic study on the level of cells,tissues organs and whole organisms confirmed that the imaging probes had good biocompatibility.The r1（6.15mM-1 s-1）,r2（13.8 mM-1 s-1）and and HU values（48.5 HU g-1）of the probes were higher than that of the common used contrast agent Gd-DTPA and Iobitridol.The distribution demonstrated that the nanoparticlesmainly accumulate in liver and spleen,and the nanoparticles could be totally excreted from the mice after 30 days injection.In addition,T1/T2-MR and CT imaging of mice showed obvious contrast enhancementin liver and spleen.Importantly,the probes achieved tumor imaging.