Preparation Of Fluorescent Nanoparticles And Their Applications In Tumor Drainage Lymph Node Imaging

Complete sentinel lymph node dissection can prevent or delay tumor recurrence to a large extent,so imaging examination of draining lymph nodes is one of the keys to successful tumor surgery.Currently,commercially available imaging agents differentiate lymph nodes from their surrounding tissues by darkening the lymph nodes,but this method can be severely interfered with by blood and tissue.In recent years,fluorescent quantum dots(QDs)such as Cd Se have also been used for lymph node imaging,but the Cd contained in them is too toxic for further application in humans?Other fluorescent carbon quantum dots and other fluorescent nanomaterials migrate slowly in lymphatic vessels and are not suitable for clinical use.Therefore,the research and development of high-performance,biocompatible imaging agents for tumor drainage lymph node is of great significance for lymph node dissection in tumor surgery,with great clinical and commercial value?In this paper,fluorescent nanoparticles with good fluorescence properties in the red light region were synthesized from elements with low toxicity,and their surface modification and dispersion were carried out appropriately to evaluate their effect in tumor drainage lymph node imaging,and the biological toxicity study was carried out.Firstly,Ag-In-S/ZnS fluorescent quantum dots(AIS/ZnS QDS)were synthesized by solution reaction,and Cu-doped indium phosphide fluorescent quantum dots(CIP/ZnS QDs)were synthesized by organic phase.Cr³⁺/Pr³⁺-co-doped ZnGa Alate long-life fluorescent nanomaterials(PLNPs)were synthesized by sol-gel method.The product was characterized by transmission electron microscopy,scanning electron microscopy,X-ray photoelectron spectroscopy,X-ray diffraction spectroscopy,infrared spectroscopy,dynamic light scattering and other techniques.The particle size,dispersion state,composition,functional groups and other information were obtained.Fluorescent nanoparticles were administered subcutaneously,intradermally,intratumoral and intravenously,followed by fluorescence imaging experiments to verify the imaging ability of tumor draining lymph nodes?After intravenous injection,the behavior of mice was observed.Blood biochemical analysis and histopathological analysis were conducted to study its toxicity.Through the above experiments,the research achievements of this paper are as follows:(1)Polypyrrolidone(PVP)dispersed AIS/ZnS QDs can be used for rapid imaging of tumor draining lymph nodes.AIS/ZnS QDs was synthesized by solution reaction and dispersed in PVP,and the hydration particle size of the product was 295nm.After subcutaneous injection,AIS/ZnS QDs presented a bright red light in mice,achieving a signal-to-noise ratio of 8.9 times?AIS/ZnS QDs could migrate to sentinel lymph nodes(axillary lymph nodes)within 15 min after percutaneous injection into the upper extremities,and to tertiary lymph nodes after percutaneous injection into the lower extremities?After intratumoral injection into H460 tumor-bearing mice,AIS/ZnS QDs could realize tumor drainage lymph node imaging within 10 min.The PVP-dispersed AIS/ZnS QDs lacked targeting and did not accumulate in the tumor after intravenous administration.AIS/ZnS QDs did not cause death,abnormal behavior,changes in blood biochemical indexes and histopathological changes,therefore high biocompatibility and low toxicity.(2)PVP dispersed CIP/ZnS QDs has a faster imaging speed of tumor draining lymph nodes.CIP/ZnS QDs was synthesized by hydrothermal method.The products were still dispersed with the same proportion of PVP,but the dispersion of CIP/ZnS QDs was better.The hydration particle size of CIP/ZnS QDs was 164 nm,which was more suitable for lymph node imaging?CIP/ZnS QDs was injected subcutaneously into the back of mice,and the fluorescence signal to noise ratio reached 7 times?CIP/ZnS QDs migrated to sentinel lymph nodes more quickly after percutaneous injection into the lower extremities.After intratumoral injection into H460tumor-bearing mice,CIP/ZnS QDs could realize tumor draining lymph node imaging within 5 min.After intravenous injection,CIP/ZnS QDs did not accumulate in the tumor,and did not cause death or blood biochemical changes in mice,nor did it cause histological changes in organs.(3)Tween 80 dispersed PLNPs not only have a fast imaging speed,but also can overcome the interference of autofluorescence,and achieve the imaging of tumor drainage lymph nodes with high SNR.PLNPs were synthesized by sol-gel method and dispersed into Tween 80 solution with a hydrated particle size of 5 nm?After subcutaneous injection,the SNR of long-life afterglow imaging in nude mice was as high as 962 times,much higher than the 5.2 times in fluorescent mode?PLNPs could reach lymph nodes quickly when injected into the lower limbs,and the signal-to-noise ratio of afterlight imaging reached 61.2 times.In the intratumoral injection experiment of H460 tumor-bearing mice,PLNPs could rapidly realize the imaging of tumor draining lymph nodes within 3 min,with a signal-to-noise ratio of 462 times.Similarly,no tumor uptake of PLNPs was observed after intravenous administration.PLNPs also had good biocompatibility and no obvious toxicity was observed.