Preparation Of Novel Multifunctional Zinc Gallium Germanate Persistent Luminescence Nanomaterials For Bioimaging And Photodynamic Therapy

Persistent luminescent nanoparticle(PLNP)has a great promise in the field of biosensing,bioimaging,cancer diagnosis and therapy due to its long-life luminescence without continuous light excitation for the elimination of auto-fluorescence interference in bioimaging.The surface functionalization of PLNP is essential for its wide application.Therefore,simple and efficient strategies for the surface functionalization of PLNP are helpful to expand its application in food safety and biomedical fields.Photodynamic therapy,as a non-invasive therapy,has attracted wide attention in cancer treatment and has been approved for multiple clinical treatment of tumors.In this dissertation,several novel multifunctional near-infrared PLNPs were fabricated for bioimaging and imaging-guided photodynamic therapy.The main research results are as follows:A triphenylphosphonic acid(TPP)conjugated near infrared luminescent PLNP nanoprobe(PLNP-TPP)was developed for mitochondrial targeted imaging in cancer cells.A near infrared Cr doped gallium zinc germanate PLNP(Zn_1.6Ga_1.6Ge_0.2O₄:Cr)was prepared by a hydrothermal method.The as-prepared PLNP has the advantages of small particle size,good dispersion,excellent near infrared emission and repeated excitations by visible light.The amino functionalized PLNP(PLNP-NH₂)was prepared by surface modification of(3-aminopropyl)triethoxysilane(APTES).Meanwhile,PLNP-TPP was prepared by conjugating TPP onto the surface of PLNP-NH₂through amidation reaction.The content of the TPP grafted on the surface of PLNP was 36?g·mg^-1.The prepared mitochondrial targeting nanoprobe PLNP-TPP had good water-solubility,photostability and biocompatibility.In addition,the as prepared PLNP-TPP can cross the mitochondrial membrane into the mitochondria of cancer cells and accumulate in the mitochondria,showing a good application prospect for mitochondrial targeted imaging.The ultrasound-assisted reduction and freezing method were employed to develop a porphyrin/G-quadruplexconjugatedAu/PLNPtheranosticnanoprobe(TCPP-GDNA-Au/PLNP)for tumor image-guided photodynamic therapy.A near infrared triple-doped gallium zinc germanate PLNP(Zn_1.25Ga_1.5Ge_0.25O₄:0.5%Cr³⁺,2.5%Yb³⁺,0.25%Er³⁺)was prepared by a surfactant-assisted hydrothermal method in combination with calcination.Gold/persistent luminescence nanocomposites(Au/PLNP)was prepared through in situ reduction of the Au(III)chelated on the surface of thiol functionalized PLNP by sodium citrate under ultrasound-assisted.PLNP was used as the core of the nanocomposites for bio-imaging without auto-fluorescence interference while Au was coated on the surface of PLNP for facile subsequent DNA conjugation.The thiol of AS1411 aptamer and the Au on the surface of Au/PLNP were conjugated via Au-S bonding at-80?to prepare a stable DNA conjugated Au/PLNP nanocomposites(DNA-Au/PLNP).This method did not need extra reagents and gave the content of DNA conjugated on the surface of Au/PLNP was 0.52nmol·mg^-1.Meanwhile,the prepared DNA-Au/PLNP kept good stability in aqueous solution in the presence of high concentration of GSH(20 mmol·L^-1).In addition,the AS1411 aptamer on Au/PLNP surface can not only recognize the over-expressed nucleolins in cancer cells specifically,but also form a G-quadruplex structure to form GDNA-Au/PLNP nanocomposites in the presence of K⁺.Further integration of GDNA-Au/PLNP and tetrakis(4-carboxyphenyl)porphyrin(TCPP)gave TCPP-GDNA-Au/PLNP for photodynamic therapy.The TCPP-GDNA-Au/PLNP nanoprobe had high ¹O₂generation efficiency for significant inhibition of tumor and good tumor-targeting ability,providing a novel image-guided photodynamic therapy for tumor treatment.The ultrasound-assisted reduction method was further employed to achieve the loading of amino-porphyrin on the silver/PLNP at room temperature and a glutathione(GSH)-responsive amino-porphyrin loaded silver/PLNP theranostic nanoprobe(p-Ag/PLNP)was developed for tumor image-guided photodynamic therapy.Ag/PLNP nanocomposites were prepared via in situ reduction of the Ag(I)chelated on the surface of thiol functionalized PLNP to Ag NPs by ascorbic acid under ultrasonication.The prepared Ag/PLNP nanocomposites not only retained the optical properties of PLNP,but also provided abundant binding sites for the subsequent loading of amino-porphyrin molecules.The amino-porphyrin molecules could be efficiently loaded on the surface of Ag/PLNP nanocomposites by shaking at room temperature via the Ag-N bonding.This method did not need additional reagents and complex reaction,and gave the content of loaded amino-porphyrin was 24.9?g·mg^-1.The93.5%of the amino-porphyrin on the surface of p-Au/PLNP could be released at high level GSH(20 mmo·L^-1)owing to the ligand exchange reaction between GSH and amino-porphyrin molecules.Meanwhile,because of the reaction between thiol group of GSH and the Ag on the surface of Ag/PLNP,it can alleviate the consumption of ROS by the thiol group and improve the PDT effect.In addition,p-Ag/PLNP had high¹O₂generation efficiency,the targeting ability to the tumor site of mice through EPR effect and the significant inhibition of the growth of cancer cells and tumor in micetumor,proving a good application prospect in image-guided photodynamic therapy.