Experimental Studies On The Application Of Graphene Quantum Dots In Ocular Tumor Imaging And Treatment

Ocular tumors include tumors of the eyelids,conjunctiva,layers of the eyeball,and ocular attachments.Benign tumors can damage the eye tissue and its function,while malignant tumors damage not only the eye and visual function,but also the orbital peripheral intracranial diffusion or systemic metastasis.Common intraocular malignant tumors,including retinoblastoma,choroidal melanoma,etc.,with a high degree of malignancy,metastasis and low age of onset,is a clinical thorny problem.Despite the significant progress made in the comprehensive treatment of ocular tumors in recent years,surgical removal of the eye is still the most commonly used treatment in clinical practice.The main reason is that when the diagnosis of ocular cancer in our country,the late number accounted for 84%,they have nissed the best time for treatment.It has great significance for the retention of patients with eyeballs,improve patient quality of life and survival rates to achieve early detection,early diagnosis of ocular tumors.In all the traditional and modern diagnostic methods,fluorescent imaging has a unique advantage of high resolution.Traditional organic fluorescent dyes have low yield(low fluorescence efficiency),wide emission spectrum(low specific)and easy bleaching.Compared with the traditional organic fluorescent dyes,Quantum dots(QDs)shows a very broad application prospects in cell markers,biological imaging,molecular diagnosis,and other fields because of their excellent optical performance.With the development of quantum dot surface modification technology,quantum dots also show great potential in the field of molecular drug targeting delivery and individual treatment.In my research,the surface functionalized modifications,biocompatibility and its application in the early diagnosis and treatment of ocular tumors are studied based on the new type N-doped graphene quantum dots,mainly including: tumor imaging with high sensitivity imaging of tumor in vitro and in vivo,anti-autophagy treatment,specific as follows:(1)The N-GQDs are prepared via the polymerization of 2,3-diaminophenazine(DAP)by hydrothermal treatment.The FN-GQDs(folic acid loading 14 wt.%)are further fabricated via hydrothermal treatment of the mixed aqueous solution of N-GQDs and folic acid.The parameters of size,element composition,covalent bond,electric potential and fluorescence intensity of FN-GQDs are evaluated.Subsequently,retinoblastoma Y79 cell line and choroid melanoma OCM-1 cell line are selected respectively,and the experiment confirms that the new FN-GQDs can be used for fluorescence labeling and imaging of ocular tumors Y79 and OCM-1.In addition,in the model of subcutaneous tumor of nude mice,FN-GQDs can be aggregated into the tumor to perform effective tumor imaging.(2)An anti-autophagy therapy stragey of FN-GQDs combined with autophagy inhibitor(Chloroquine,CQ)was established.In the proteomics,we find that FN-GQDs can obviously induced tumor cell autophagy levels,through the introduction of autophagy inhibition molecules.FN-GQDs induce the apoptosis pathway to realize the tumor cells killing.In the subcutaneous tumor of nude mice model,the treatment is effective to reduce the volume of the tumors,improve the survival rate of the nude mice.In addition,real-time monitoring and assessment of the treatment process can be realized by the imaging system in vivo.In conclusion,a novel folate functionalized modified N-doped graphene quantum dot was constructed which realized the fluorescence imaging and visualization treatment of ocular tumor from cell level and animal level,and it laid a theoretical foundation for early diagnosis and targeted therapy of ocular tumors.