Antitumor Properties Of Highly Doped Rare Earth UCL/NIR Ⅱ Luminescent Nanomaterials

Rare-earth up-conversion nanocrystals are able to emit high energy photons under excitation by near-infrared（NIR）light,referring to a nonlinear optical upconversion process in which the sequential absorption of two or more photos leads to the emission of light at shorter wavelengths than the excitation photons.Up-conversion nanocrystals have many advantages,such as adjustable emission peak,high fluorescence stability,narrow emission peak width,long life,relatively low cytotoxicity and little background interference,making them attractive contrast agents in optical biomedical imaging and detection.In this dissertation,we systematically explored the application of highly doped rare earth up-conversion nanocrystals in tumor treatment and biological imaging,and demonstrated the unique properties and advantages of rare earth upconversion luminescent nanomaterials in biological applications.The specific research results are as follows:Chapter 1:Recent research propresses of using UCNP for biomedical applications are reviewed in this chapter.The motivations of research in this dissertation are discussed.Chapter 2:Generally,luminescence quenching at high doped concentrations typically limits the concentration of doped ions in the lanthanide material to less than 0.05-20 mol%,and this is still a major hindrance in designing nanoplatforms with improved brightness.In this research,a nanoplatform capable of dual-modal imaging and synergetic antitumor cells therapy was designed.NaYF₄:x%Er@Na XF₄（x=5,25,50,100,X=Lu and Y）core@shell nanoparticles with Er³⁺ions concentration up to 100 mol%were synthesized and the luminescence properties under near-infrared（NIR）excitation were detected.The results protrude the strong coupled of surface and concentration quenching effects in upconversion nanoparticles（UCNP）.Upconversion luminescence（UCL）and NIR Ⅱ emission intensity increased with negligible concentration quenching effect under 980 and 800 nm NIR lasers because of the growth of epitaxial shells.Chapter 3:In this research,a multi-modal imaging platform guided photodynamic theranostics under 808 nm was designed using a NaErF₄:Tm@NaYF₄:Yb@NaLuF₄:Nd,Yb-Zn Pc structure.Unlike conventional co-doped Yb³⁺/Er³⁺system,Er³⁺ions as activator and sensitizer were used to improve the up-conversion energy transfer processes.Furthermore,higher energy transfer processes between Er³⁺ions could be obtained through doped 1%Tm³⁺ions as an energy trapping center in the NaErF₄.This platform could emit much brighter upconversion luminescence（UCL）（124-fold enhancement for red emission）and near-infrared II（NIR Ⅱ）emission under single 808 nm laser excitation.Importantly,the NIR Ⅱ imaging with higher resolution and better signal-to-noise can pass the blood brain barrier to see the brain vessels.Due to the enhanced red emission,the UCL nanoparticles were combined with Zn Pc agent to exhibit photodynamic therapy（PDT）effect,and its distribution and excretion could be detected by the photoacoustic（PA）imaging under single NIR laser.Thus,this platform could be used as multi-modal imaging（NIR Ⅱ,PA,CT,and UCL）guided PDT agent under single 808 nm laser.Chapter 4:In this research,a p H-sensitive degradable nanoprobe was designed by combining hydrophobic rare earth nanoparticles with biocompatible m PEG-PLGA nanomicelles for NIR Ⅱ luminescence guided anti-cancer chemo-therapy.The as-synthesized nanoprobes（about 200 nm）with highly enhanced permeability and retention（EPR）effect show great potential in the diagnosis of solid tumors,providing new prospects for clinical tumor diagnosis.Then,the degradable composite probes increase the imaging sensitivity of the probe and allow for slow release of the internal tumor drugs,reducing the loss of the drug during delivery.Finally,the ultra-small rare earth nanoparticles（about 6 nm）can be excreted after hydrolysis of the composite probe to reduce the enrichment of the inorganic nanoparticles in vivo.Thus,this degradable NIR Ⅱ imaging probes based on polymer-lanthanide composite could be a promising candidate for preclinical cancer chemotherapy and surgery navigation under a single 808 nm laser.In summary,this thesis develops a series of tumor treatment and bioimaging methods based on rare earth up-conversion luminescent nanomaterials,and systematically studies the biological applications of highly doped rare earth nanomaterials,including multimodal biological imaging and tumor treatment.At the same time,a new method of surface-modified hydrophobic-based rare earth nanoparticles was also introduced to synthesize a degradable"sesame cluster"structured probe.