The Biological Applications Of Multifunctional Upconversion Composite Nanoparticles

With the rapid advances in the nanotechnology, the development of multifunctionalnanoparticles has drawn attentions of many researchers, promising a broad range ofbiomedical applications. Among them, early diagnosis of cancers aided by imagingtechnologies and new therapies such as photothermal therapy (PTT) are very importantexamples. Others include nano systems responsive to external stimulus and able torelease drugs/signaling molecules in a controlled manner. This thesis describes myefforts in developing multifunctional nanoparticles for two biomedical applications,including:First, I developed an approach of synthesis and bioconjugation of multifunctionalnanoparticles (UCNP-Fe3O4-Au-antibody) for cancer imaging and photothermal therapy.A layer-by-layer assembling technique was employed to construct multifunctionalnanoparticles, composed of poly(acrylic) acid modified upconversion nanoparticles(180nm), dopamine modified superparamagnetic nanoparticles (6~9nm), and gold shell(Au) through electrostatic interactions. Monoclonal antibody (Anti-HER2) wasconjugated onto the surface of MFNPs through EDC-NHS coupling. I demonstratedsuccessful detection and imaging of the target cancer cells (BT474) using upconversionluminescence, producing signals with high SNR. These multifunctional nanoparticleswere then applied for PTT because of strong surface plasma resonance absorption ofgold shell. Our experiments suggested that the outcomes after PTT correlated well withthe heterogeneity of the cancer cells (for example, the differential expression of antigenon the cell surface). On the other hand, our image data supported that PPT can beperformed at the single cell level, induced by the antigen-antibody recognition events.Second, I developed an interesting strategy of releasing small molecules of gas(NO) switched by NIR lumination. The rare-earth doped upconversion nanoparticleswere coated by silica (SiO2), and then conjugated with a nitric oxide donor-SNAP, thusforming a structure of UCNP-SiO2-SNAP. These nanoparticles displayed an interesting property enabling energy conversion from NIR to UV lamination, thus breaking thechemical bonds of SNAP molecules and releasing nitric oxide in a light-controlledmanner. I demonstrated that this approach can be applied to inhibit platelet aggregationwith a980nm laser.In summary, this thesis presents my studies on detecting cancer cells, andsimultaneous photothermal treatment with MFNPs; a pilot study on biomedicalapplications with gas molecule releasing switched by NIR lamination. These results willassist paving a new avenue to fulfill the unique properties and applications of MFNPs inbiomedicine.