Precise Diagnosis And Treatment Of Glioma Based On Rare Earth Dual-Mode Conversion Nanomaterial

Glioma,as the most aggressive neurological tumor,gradually exhibit on a youthful trend and the 5-year survival rate of patients is low.Current clinical treatments（surgery,radiotherapy and chemotherapy）for glioma have significant drawbacks,so it is crucial to develop alternative treatments with higher specificity and therapeutic efficiency.Photodynamic therapy with high accuracy and minimal invasiveness has been widely used to treat diseases,however,the treatment of malignant tumors in deep locations has yet to be developed due to the limitation of optical penetration depth.In addition,due to the infiltrative growth characteristics of gliomas,it is difficult to define tumor boundaries and identify microinvasive foci.Therefore,the design and development of NIR-II fluorescent probes with lower tissue autofluorescence,higher signal-to-noise ratio and deeper biological tissue penetration has become an important research direction.In this paper,the rare earth dual-mode conversion nanomaterials,which have near-infrared excitation,good photostability and tunable emission,were used to improve hydrophilic and target ability by surface modification with amphiphilic polymers and glioma-targeting neuropeptide Y₁ ligands.Then equipped with aggregation-induced luminescent small-molecule photosensitizers,RENPs@TIND-^DAPT-NPY is constructed as the novel targeted nanocomposite based on rare earth dual-mode conversion nanomaterials.By effectively utilizing the unique properties of the up/down-conversion luminescence under single-wavelength laser excitation,we further explore its application in the diagnosis and treatment of glioma.The main research contents are summarized as follows:（1）Through research on investigating the optical properties and surface modification of NaGdF₄:Nd³⁺（3 mol%）,Yb³⁺（2 mol%）,Tm³⁺（0.3 mol%）nanoparticles doped with three kinds of rare earth ions,Nd³⁺,Yb³⁺,and Tm³⁺,it is found that they can simultaneously generate up/down dual-mode conversion luminescence under the excitation of a single wavelength of 808 nm.The synthesized nanoparticles not only have great hydrophilicity and photostability,but also achieve the NIR-II fluorescence imaging,and the tissue penetration depth can reach 10 mm.Subsequently,the functions of photodynamic therapy and NIR-II fluorescence imaging are endowed to the material by loading the aggregate induced emission molecular photosensitizer TIND and surface modification with neuropeptide Y₁ ligand,which is verified by a series of experiments such as reactive oxygen species detection and fluorescence imaging.（2）Cell experiments show that the RENPs@TIND-^DAPT-NPY nanocomposite can generate cytotoxic reactive oxygen species under 808 nm laser irradiation,and has obvious therapeutic effect on glioma cells（U87-MG cells）.Animal experiments reveal that the RENPs@TIND-^DAPT-NPY nanocomposite have great biocompatibility in vivo.After tail vein injection,NIR-II fluorescence imaging could clearly identify the location of orthotopic glioma,and the tumor signal-to-background ratio reaches 5.0.Meanwhile,under the guide of imaging,photodynamic therapy could significantly inhibit the growth of gliomas,reaching an 80%survival rate within 30 days,compared with all deaths in the control group.