Development And Application Of Near-Infrared Persistent Luminescence Nanoprobes For Biosensing And Imaging

The development of probes for biomolecule detection and imaging is a highly active research area.Among different detection methods,optical sensing technology is a non-invasive imaging technology for real-time imaging.Due to its advantages such as short response time,high sensitivity,easy operation and low cost,it has attracted more and more attention.However,traditional optical measurement methods based on organic fluorescent probes or inorganic fluorescent nanoparticles suffer from the interference of autofluorescence,light scattering from biological fluids and tissues,and photobleaching of organic fluorophores,leading to low sensitivity and signal-to-noise ratios in biological analysis.Persistent luminescence materials can still emit light lastingly after stopping excitation.Autofluorescence interference can be effectively eliminated by collecting persistent luminescence signals,which can significantly improve imaging contrast and detection sensitivity.In addition,near-infrared（NIR）light-emitting persistent luminescence materials show low scattering and absorption coefficients in penetrating biological organs or tissues,and do not require continuous excitation light irradiation,which can effectively reduce the damage caused by light irradiation to tissues.However,because of the poor targeting of biomolecules by traditional optical sensors,it is urgent to develop substances that target biomolecules with high specificity to improve the specificity and selectivity of detection.Nucleic acid aptamer is a powerful choice for detecting cancer markers.It has the advantages of easy in vitro synthesis,high stability and good repeatability.It is often used in molecular detection.Therefore,aptamer-modified persistent luminescence materials with NIR light emission provide broad application prospects in the fields of biosensing and bioimaging.In this artical,we firstly synthesized NIR persistent luminescence nanoparticles by hydrothermal method.Based on the synthesized NIR persistent luminesc ence and the highly targeted aptamer,we further constructed aptamer-guided persistent luminescence nanoprobe.Applications of the aptamer-guided persistent luminescence nanoprobe in biosensing and bioimaging were explored and the specific research contents are as follows:（1）Zn_1.2Ga_1.6Ge_0.2O₄:0.5%Cr（ZGGO:Cr）persistentluminescence nanoparticles with NIR light-emitting were synthesized by hydrothermal method.The excellent luminescent properties of materials were validated by fluorescence spectrophotometer and IVIS Lumina XR imaging system,which sustained luminous time up to 8 h.At the same time,based on the good luminescence properties of persistent luminescence materials,it is used for cell imaging.Because of the large overlap between emission spectrum of persistent luminescence nanoparticles and absorption spectrum of BHQ3 dye molecules,ZGGO:Cr nanoparticles serve as NIR light-emitting units and BHQ3 dye molecules serve as quenchers based on the principle of Fo?rster resonance energy transfer.Persistent luminescence nanoprobes（ZGGO:Cr-Apt）were constructed using ZGGO:Cr and BHQ3,which functionalized with prostate specific antigen（PSA）Apt and its complementary cDNA,respectively.This aptamer-guided persistent luminescence nanoprobe can achieve high sensitivity and specificity to detect PSA,which has great significance for the early diagnosis of prostate cancer.（2）In order to get the dual-function ZGGO:Cr-Apt@Lip-AL nanoprobes,ZGGO:Cr-Apt nanoprobes were loaded into the acid-responsive liposome（Lip）,which modified by specific targeted bone tissue alendronate（AL）.The prepared dual-function ZGGO-Apt@Lip-AL nanoprobes can be used for the detection and imaging of PSA in the microenvironment of prostate cance r bone metastases.Transmission electron microscopy and atomic force microscopy show that the ZGGO:Cr-Apt@Lip-AL nanoprobe was prepared successfully.The ZGGO:Cr-Apt@Lip-AL nanoprobe not only responds to the acidic microenvironment,but also has strong tar geting to hydroxyapatite.At the same time,the laser confocal microscopy imaging proved that the ZGGO:Cr-Apt@Lip-AL nanoprobe could real-time imaging of prostate cancer cell PC-3 migration and acidic microenvironment.Thus,this work provides an advantage ous means for the early detection and long-term monitoring bone metastases in prostate cancer and promotes the development of imaging-guided surgery and treatment that targeted metastatic bone tumors in the future.