Fabrication Of Near-infrared Emitting Persistent Luimenescent Nanoprobes For Bioimaging

The applications of molecular probe in biomedical imaging are more important for noninvasive in vivo visualization and measurement of the biological processes at the cellular and molecular level, understanding of the mechanisms and characteristics of the disease at the molecular level, and early diagnosis and treatment of the disease. The syntheses and applications of molecular probe have attracted researcher’s great attention. Compared to other imaging technologies, the optical imaging with the fluorescent probes have many adventages, such as high sensitive, low cost, portable, time effectiveness and no harmful radiation, but remains high background noise and low penetration depth. The near-infrared (NIR) emitting persistent luminescent nanoparticles (PLNPs) have a long NIR afterglow time, and no need for in situ excitation during the biomedical imaging. Thay not only can completely avoid tissue autofluorescence, light scattering and phototoxicity originating from the excitation source, but also have deeper tissue penetration, due to their emission wavelenght located in the NIR region of the "biological window". Furthermore, the combination of the NIR emitting PLNPs and the magnetic resonance imaging (MRI) contrast agents in a single nanoparticulate platform have advantages of high sensitivity, high spatial resolution and no ionizing radiation for biomedical imaging. The purpose of this thesis is developing of the molecular probe based on the NIR emitting PLNPs for biomedical imaging. The novelty and main contents of the thesis are summarized as follows:(1) The NIR-emitting PLNPs based on Cr3+/Pr3+codoped zinc gallogermanate (Zn2.94Gai.96Ge2O10:Cr3+0.01, Pr3+0.03) were developed by a citrate sol-gel method with a subsequent reducing atmosphere-free calcination. The persistent luminescence of the PLNPs is significantly improved via codoping Cr3+/Pr3+and creating suitable Zn deficiency. A persistent energy transfer between zinc gallogermanate host and Cr3+ion in the PLNPs is observed and its mechanism is discussed. The PLNPs exhibits bright NIR luminescence with a superlong afterglow time of over360hours, and have a great potential as a molecular probe for in vivo deep tissue imaging with the absence of background noise.(2) An active targeting molecular probe based on NIR-emitting PLNPs was developed for in vivo targeted tumor imaging. The surface modification of PLNPs with a3-amino propyltriethoxysilane (APTES) and a poly ethylene glycol greatly improves the biocompatibility and the water solubility of nanoprobe. Further conjugation of the nanoprobe with a targeting molecule of RGD peptides was carried out for targeted imaging of the αβν3integrin overexpressing U87MG cells and the U87MG tumor-bearing nude mice. The NIR persistent luminescence properties and the NIR photostimulation abilities of the PLNPs based molecular probe were investigated in the living animal tissue. The PLNPs based probe allowed in vivo bioimaging for more than450min without the need for in situ excitation, and holding great potential for long-term in vivo targeted bioimaging application with high signal-to-noise ratio (SNR).(3) A novel class of multimodal imaging probe based on the NIR-emitting PLNPs was developed for in vivo T1-weighted MRI and NIR luminescence imaging. The combination of the ATPES modified PLNPs with the gadolinium complexes not only preserves the excellent NIR persistent luminescence property of PLNPs, but also brings the paramagnetic property of higher longitudinal relaxivity (6.72mN-1s-1) than the commercial contrast agent Gd(Ⅲ)-diethylenetriamine pentaacetic acid complexes. The results of in vivo dual-modal imaging indicate that the as-prepared multimodal probe Gd(Ⅲ)-PLNPs have the complementary advantages of the MRI and the NIR persistent luminescence imaging. Moreover, the present combination provides new opportunities for in vivo biomedical imaging with high sensitivity, spatial resolution and SNR.