Fabrication Of Cyclodextrin-functionalized Upconversion Nanoparticles And Bioanalysis Application

Upconversion nanparticles (UCNPs), which emerged as novel biolabelling probes,have caught the attentions of the researchers in the field of biomedical imaging.Different from conventional fluorescent labels, such as organic dyes or quantum dots,upconversion process is based on sequential (not simultaneous) absorptio n oftwo-photon or multiphoton, converting low frequent exciting light into high frequentemitting light. In other words, near-infrared light exciting UCNPs can effectivelyavoid the disturbing from aZYSfZSW Xc Rc WSQ bMSPSKMcaP samples, thus improvinganalytical sensitivity and signal-to-noise ratio. Besides, near-infrared light possessesdeeper penetration and smaller light damage on biological samples. Moreover, UCNPsdisplay other advantages such as low toxicity, good photostability, large stokes shiftand being excited by near infrared laser, successfully applying to the detection andimaging of gas, ions and biomolecules, et al. Therefore, UCNPs possess broadapplication prospect in the fields of biomarkers and bioassays. To date, however, ratherlow solubility in water and unsuitable surface property are the primary problemsrestricting their development in biomedical field. Because UCNPs synthesized viasolvothermal are capped by oleic acids on the surface, hydrophobic UCNPs used asbiological luminescent labels should be water-soluble via surface functionalization forbioimaging applications. The reported surface functionalization strategies confine thefurther bioconjugation of UCNPs and some surface ligands have potential toxicity,restricting their development in biomedical field. To settle this problem, in thisdissertation we used highly biocompatible and hydrophilic-cyclodextrins as theligands to anchor the surface of UCNPs via ligands exchange and covalentmodification, achieving targeting tumor biolabelling and detection of NO. Specificresearch content are as follows:1. Fabrication of cyclodextrin-functionalized upconversion luminescencenanoplatform and imaging of tumor-cyclodextrins and their derivatives, well known as excellently biocompatibleand hydrophilic molecules, are widely used in food, pharmaceutical and drug delivery.Besides,-cyclodextrins is a widely used host molecule capable of internalizing guestmolecules in water. Therefore, in this chapter we used6-phosphate-6-deoxy--cyclodextrins (PCD) as surface ligands to modify hydrophobic UCNPs. Water-dispersible PCD/UCNPs can be easily obtained throughtwo steps (ligands exchange and click chemistry) from hydrophobic organic phasebecause phosphonate groups of PCDs have greater affinity to the surface oflanthanide-based nanoparticles and then, replace carboxylic acid groups of oleic acidligands. Therefore, water-soluble versatile upconversion luminescent nano-platformcan be achieved. Based on this platform, we estimated the coverage rate of PCDs onthe surface of UCNPs and studied its permeability, stability and toxicity in cells.Moreover, we demonstrated the versatility of nanoplatform by the host-guestinteraction of rhodamine B conjugated adamantane and aspartate-riched peptide chainconjugated adamantane. Finally, we displayed the application of upconversionnanoplatform as a targeting bioprobe to label cervical cancer cells and tissue.2. Fabrication of cyclodextrin-functionalized upconversion nanoprobe fordetection of NONO as the widespread signaling molecule in the organisms, has importantphysiological and pathological significances. Currently, the fluorescence imagingmethods to NO in vivo suffer from low penetration depth, photobleaching, biologicalbackground fluorescence interference et al. Recently, UCNPs with antistokes shiftemission characteristics have been considered as a kind of excellent biomarker due tothe advantages of narrow emission peaks, tunable optical properties, higher penetrationdepth in tissue, zero biological background interference and so on. In view of theexisting problems in biological imaging of NO, this chapter usecyclodextrin-functionalized upconversion nanoparticles as near-infrared-lightmediated illuminant and rhodamine B as NO probes. Afterwards, we connectedrhodamine B to adamantane, which has strong host-guest interaction with-cyclodextrins, so that we can combine UCNPs as near-infrared excitation lightsources and organic molecule probes as bio-recognition components to developupconversion luminescent nanoprobe to detect NO based on the strategy offluorescence resonance energy transfer. Finally, we successfully detect NO via thenanoplatform we fabricated.