Upconversion Nanoparticles For Biomedical Imaging And Therapy

Rare earth upconversion nanoparticles (UCNPs) are able to emit high-energyphotons under excitation by near-infrared (NIR) light, referring to a nonlinear opticalupconversion process in which the sequential absorption of two or more photons leadsto the emission of light at shorter wavelengths than the excitation photons (anti-Stokesemission). The upconversion luminescence (UCL) from UCNPs exhibits a range ofunique properties, such as sharp emission bandwidths, long lifetime, tunable emission,high photostability, low cytotoxicity, and importantly, little backgroundauto-fluorescence, making them attractive contrast agents in optical biomedicalimaging and detection.In this dissertation, we further explore the applications of UNCPs and theirnano-composites in imaging-guide tumor therapy, stem cell labeling and tracking, aswell as detection of circulating tumor cells. Specific research results are as follows:Chapter1: Recent research progresses of using UCNPs for biomedical applicationsare reviewed in this chapter. The motivations of research in this dissertation arediscussed.Chapter2: Drug delivery with upconversion nanoparticles for multi-functionaltargeted cancer cell imaging and therapy. We functionalize UCNPs with a polyethyleneglycol (PEG) grafted amphiphilic polymer. The PEGylated UCNPs are loaded with acommonly used chemotherapy molecule, doxorubicin (DOX), by simple physicaladsorption via a supramolecular chemistry approach for intracellular drug delivery.TheUCNP drug loading strategy could provide a facile and flexible way to load anddelivervarious therapeutic moleculesfor cancer imaging and therapy.Chapter3: Near-infrared light induced in vivo photodynamic therapy (PDT)of cancerbased on upconversion nanoparticles.We load Chlorin e6(Ce6), a photosensitizer, ontoNaFY4-based UCNPs functionalized with PEG, forming a supramolecular UCNP-Ce6 complex which is used for NIR light-induced PDT treatment of tumors in an animalmodel. We for the first timedemonstrate the highly efficient NIR-inducedPDT oftumors in a mouse model using UCNPs. Such strategy offers remarkably enhancedtissue penetration in comparison to traditional PDT. Our work provides an encouragingalternative to circumvent limitations of current photodynamic therapies which aretriggered by visible light.Chapter4:Imaging-guided pH sensitive photodynamic therapy using chargereversible upconversion nanoparticles under NIR light.A layer-by-layer (LbL)self-assembly strategy is employed to load multiple layers of Ce6conjugated polymersonto UCNPs via electrostatic interactions.By further coating UCNP with an outer layerof charge-reversible polymer, we for the first time realize pH-responsive PDT using PSmolecules loaded with charge-reversible UCNPs, for dual-modal imaging-guidedNIR-excited PDT cancer treatment.Chapter5: Oligo-arginine modified upconversion nanoparticles for stem cellslabeling and ultra-sensitive in vivo tracking.We use oligo-arginine conjugatedUCNPsto effectively label mouse MSCs (mMSCs), whose proliferationanddifferentiation potentials are found to be not noticeably affectedafterUCNP-labeling. Down to nearly the single cell level of in vivo tracking sensitivity isthen realized for UCNP-based mMSCs.Chapter6: Multifunctional upconversion nanoparticles (MFNPs) for dual-modalimaging guided stem cell therapy under remote magnetic control.MFNPs based on Aushelled UCNP-iron oxidenano-composites with unique optical and magnetic propertiesare synthesized and then used to label mMSCs.Highly sensitive in vivo tracking ofMFNP-labeled mMSCs is realized in vivo by UCL imaging. More interestingly, wefurther demonstrate that the translocation of MFNP-labeled mMSCs could becontrolled by external magnetic field, which is able to induce the accumulation ofmMSCs into the targeted lesion and promote tissue repairing. Our work promisesfuture explorations of multifunctional nanoprobes in stem cell research.Chapter7: Detection of circulating tumor cells (CTCs) with upconversion multifunctional nanoparticles and silicon nanowire array based microfluidic technique.CTCs are captured by antibody labeled MFNPs and enriched under the magnetic fieldwhen following through the microfluidic channel, in which Si nanowire array substrateis incorporated to increase the capture efficiency. Highly efficient CTC capture anddetection is then demonstrated not only withartificial samples, but also with clinicalsamples collected from cancer patients.In summary, this thesis illustrates a comprehensive investigation of UCNPs andUCNP-based composite nanostructures for applications in imaging-guided therapy,stem cells labeling&tracking, and CTC detection. Our results greatly promise furtherexplorations of those functional nanomaterials in biomedical research.