| Summary: | Cancer, a generic group of diseases, can affect distant sites of the human body to cause sever health consequences. According to the World Health Organization, 9.8 million people died from cancer in 2015 worldwide, about 1600 people per day. More seriously, the number of new cases is expected to increase 70% by 2030 to cause 12 million deaths globally. Early detection, accurate diagnosis and effective treatment are crucial in increasing cancer survival rates and reducing patients’ suffering. In particular, precise cancer positioning that can guide surgery, chemotherapy and radiotherapy has important clinical significance in successful treatment. The nanotechnology-based diagnosis (e.g. QD/QR-bioconjugate probes) and/or treatment of different cancers have received great attention, which is growing to be a promising field in medical research. Over the past 20 years, not only have QD based probes been widely used in developing immunoassays, cellular labeling, cellular imaging, tissue imaging and in vivo imaging, but also being extended to researches such as the drug target and drug delivery system. And this thesis is composed of two parts: Part I An ultra-efficient ligand-exchange protocol (UCEP) to render commercial hydrophobic QDs completely water-soluble using >50-fold less of the air-stable lipoic acid (LA) based functional ligands with a rapid in situ reduction by tris(2-carboxylethyl phosphine, TECP) has been developed. The resulting water-soluble QDs are compact (Dh <10 nm), bright (retaining >90% of original fluorescence), resisting nonspecific adsorption and displaying good stabilities in biological buffers even with high salt contents (e.g. 2 M NaCl), making them well-suited for cell imaging and ratiometric biosensing. A DHLA-zwitterion capped QD prepared by the UCEP is readily biofunctionalized with hexa-histidine (His8)-tagged small antibody mimetic proteins (also known as Affimers), allowing for rapid, ratiometric detection of its target protein down to 5 pM via the QD-sensitized Förster resonance energy transfer (FRET) readout signal. Moreover, compact biotin functionalized QDs are prepared by a facile, one-step cap-exchange process for ratiometric quantitation detection of 5 pM protein such as NeutrAvidin as well as for fluorescence imaging of target model cancer cells. Part II A stable, water-soluble rod-shaped fluorescence semiconductor nanocrystal (CdSe/CdS core/shell quantum rod, QR) was made by an efficient cap exchange protocol as described in Part I. However, in most cases the fluorescence of the cap-exchanged QR was almost quenched, hindering their biomedical applications. Herein I have solved this problem by discovering a simple method that allows for efficient recovery of the QR quantum yield, making them suitable for biological applications. The resulting water-soluble QRs are compact (Dh < 20 nm), bright (recovering to > 67% of original fluorescence), resisting nonspecific adsorption and displaying good stabilities in biological buffers, making them well-suited for ratiometric biosensing. After tris(2-carboxylethyl phosphine, (TECP) reduction, a dihydrolipoic acid-zwitterion ligand (DHLA-ZW) capped QR was self-assembled with (His8)-tagged anti-yeast SUMO non-antibody binding proteins (nABPs), allowing for ratiometric detection of its target protein down to 5 pM by the QR-sensitized Förster resonance energy transfer (FRET) signal. Furthermore, compact biotin functionalized QRs are prepared by a facile, one-step cap-exchange process for ratiometric quantitation of labelled neutravidin down to 5 pM. Such sensitivity is among the very best for QR-FRET based biosensors.
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