Rare Earth Fluoride Upconversion Nanoparticles For Sensing And Therapy Applications

Rare earth doped upconversion nanoparticles（UCNPs）show special anti-stokes shift which can convert low-energy excitation light to high-energy emission light via dual/multi-photon mechanism.UCNPs have showed many advantages,such as low toxicity,high chemical stability,great light stability,large stokes shifts,narrow emission bands.Simultaneously,near-infrared（NIR）irradiation has lower photo damage effect,a large penetration depth in tissues,and at the same time,it can avoid the auto-fluorescence interference of biological sample and light scattering phenomenon,which can reduce background light and improve signal-to-noise ration.All of these advantages make them a new generation of nanomaterials in sensing,bioimaging,drug release and therapies.After combined with other functional materials,UCNPs show bright prospect in biological chemistry and clinical research.My thesis is focused on the UCNPs functionalized with other specific molecules and nanomaterials,and composed of two parts as following:1.Iron ion(Fe³⁺)which is the physiologically most abundant and versatile transition metal in biological systems,has been closely related to many certain cancers,metabolism,and dysfunction of organs,such as the liver,heart,and pancreas.In this Research Article,a novel Nile red derivative（NRD）fluorescent probe was synthesized and,in conjunction with polymer-modified core-shell upconversion nanoparticles（UCNPs）,demonstrated in the detection of Fe³⁺ion with high sensitivity and selectivity.The core-shell UCNPs were surface modified using a synthesized PEGylated amphiphilic polymer(C₁₈PMH-mPEG),and the resulting mPEG modified core-shell UCNPs（mPEG-UCNPs）show good water solubility.The overall Fe³⁺-responsive upconversion luminescence nanostructure was fabricated by linking the NRD to the mPEG-UCNPs,denoted as mPEG-UCNPs-NRD.Inthenanostructure,thecore-shellUCNPs,NaYF₄:Yb,Er,Tm@NaGdF₄,serve as the energy donor while the Fe³⁺-responsive NRD as the energy acceptor,which leads to efficient luminescence resonance energy transfer（LRET）.The mPEG-UCNPs-NRD nanostructure shows high selectivity and sensitivity for detecting Fe³⁺in water.In addition,benefited from the good biocompatibility,the nanostructure was successfully applied for detecting Fe³⁺in living cells based on upconversion luminescence（UCL）from the UCNPs.Furthermore,the doped Gd³⁺ion in the UCNPs endows the mPEG-UCNPs-NRD nanostructure with effective T₁ signal enhancement,making it a potential magnetic resonance imaging（MRI）contrast agent.This work demonstrates a simple yet powerful strategy to combine metal ion sensing with multimodal bioimaging based on upconversion luminescence for biomedical applications.2.A multifunctional cancer therapy nanocomposite was proposed and synthesized by linking pH-responsive SH-PEG-DOX prodrug onto gold nanocrystals that were grown in situ on the surface of upconversion nanoparticles（UCNPs）.In the structure of SH-PEG-DOX prodrug,a hydrazone bond was utilized for the following pH-responsive drug release in the intracellular acidic microenvironment of cancer cells.The innovative assembly method is facile and mild to obtain the nanocomposites of UCNPs and gold,which show excellent photostability and biocompatibility.The final UCNPs@Au-DOX nanocomposites offer efficient treatment effects in vitro under irradiation of a 808 nm laser due to the synergy effect of chemotherapy and photothermal therapy.In addition,the UCNPs@Au-DOX nanocomposites show excellent intracellular locating ability via upconversion luminescence（UCL）imaging by Er³⁺ion and magnetic resonance imaging（MRI）by Gd3+ion,which is potential as visual tracking agent in cancer treatment.Therefore,thepresentedbioimagingguided-multifunctionalsynergistictherapy nanocomposites are promising tools for imaging guided cancer therapy.