Preparation, Properties And Biomedical Applications Of Infrared Upconversion And Absorption Nanomaterials

Functional nanomaterials that can be excited by near-infrared light(NIR) or absorb infrared(IR) light have attracted great interest, because IR light has low energy, deep tissue penetration depth, low autofluorescence, and is less harmful to bio-tissues. They have been widely used in bioimaging, biodetections, photodynamic therapy, etc. To promote the clinical practice of these nanomaterials, it is critical to control their composition and structure, get a thorough understanding of the luminescence mechanism, and obtain highly efficient, reliable optical signals. Therefore, on the basis of the control of Yb3+/Er3+ co-doped Na YF4 upconversion nanoparticles(UCNPs) and the optimization of their luminescence properties, we constructed a theoretical model for the energy transfer mechanism between UCNPs and photosensitizers, and studied the upconversion bioimaging in 3-dimensional multicellular tumor spheroid(MCTS) with chick embryo chorioallantoic membrane(CAM) to mimic the tumor growth environment in human body. Besides, we conducted biodetection by using the characteristic IR absorption signals of Si O2 nanoparticles for the first time. It brings some convenience to the design and fabrication of nanomaterials. The details are as follows:(1) Aiming at the key scientific issue that the development of upconversion nanomaterials is constrainted by the low upconversion efficiency, we optimized the current high-temperature oil-phase synthesis methods, and prepared uniform, shell thickness controllable, and highly luminescent Na YF4:Yb3+, Er3+@ Na YF4 core/shell structured UCNPs. The precursors, surfactants, solvents, reaction times and the order chemicals added were found to have great impact on the morphology, crystal structure and luminescence properties of UCNPs. In comparison with the heat-up method, Ostwald ripening method makes it easier to obtain uniform, shell thickness controllable, pure hexagonal phase and highly luminescent core/shell UCNPs. This study provides the theoretical and material basis for the study of upconversion luminescence properties and biomedical applications.(2) To have a better understanding of the energy transfer mechanism involvingupconversion nanomaterials, we studied the effect of the shell thickness on energy transfer performance systematically, with core/shell structured Na YF4:Yb3+, Er3+@ Na YF4 UCNPs as the energy donor and Rose Bengal(RB) as the energy acceptor. A theoretical model for the energy transfer process was built based on analysis of the time behavior of both the donor and acceptor. The results showed that the strongest RB emission, which was more than ten times that of core-RB sample, occurred in the sample with Na YF4 shell thickness of ~4.2 nm. It results from the interplay between non-radiative F?rster resonance energy transfer(FRET, ~32%) and emission/reabsorption(~68%) processes. In this model, the emitting centers in the inner layer of UCNPs mainly participate in reabsorption, while the emitting centers approaching the surface participate in both FRET and reabsorption. The contribution rates of these two processes were shell thickness dependent. The(semi)-quantitative analysis of the influence of FRET and reabsorption on energy transfer performance involving upconversion nanomaterials provides some guidance to the applications of upconversion nanomaterials in homogeneous immunoassays, bioimaging, photodynamic therapy, etc.(3) Conventional in vitro cell experiments do not possess the 3-dimensional morphology of tumor, so it can only be studied on a 2-dimensional mono-layer cell plane. While in vivo imaging tends to be affected and restricted by various complicated factors from surroundings, which makes it difficult to study one single process in real-time. Therefore, we used MCF-7 MCTS as a 3-dimensional tumor cell model, and CAM as the tumor transplant recipient to mimic the tumor growth environment, and studied the biocompatibility of rare-earth ion doped upconversion nanomaterials and upconversion luminescence imaging in tumor. The results showed that polyallylamine(PAAM) modified Na YF4:Yb3+, Er3+ UCNPs have greater cytotoxicity than protonated, 2-aminoethyl dihydrogen phosphate(AEP) and polyacrylic acid(PAA) modified UCNPs, which is relevant with the surface charges and the chemical nature(such as molecular weight and the length of carbon chain) of the ligand. Low-toxic PAA modified UCNPs were chosen to couple with monoclonal antibody of estrogen receptor alpha(ER-α) of MCF-7 cell by covalent interaction. The bioconjugates were further used for bioimaging in 2-dimensional cell and 3-dimensional MCTS in CAM, and the targeted labeling of cancer cells was observed in both systems. These results provide important clinical guidance to the early-stage diagnosis of cancer based on upconversion nanomaterials.(4) To simplify the fabrication of nano-bio-probe, we prepared water-soluble and biocompatible Si O2 nanoparticles with St?ber method, and studied their IR absorption properties. The TO-LO phonon modes of asymmetric stretching of Si–O–Si bridges were proved to be characteristic. We then designed a sandwich-structured immunoassay system, and realized sensitive detection of proteins by detecting the characteristic IR absorption signals of Si O2 nanoparticles. This study provides novel ideas for the selection of IR absorption probes.