Hydrothermal synthesis of near-infra-red emitting quantum dots for fluorescent and magnetic bimodal imaging

Synthesis and characterization of water dispersible, near-infra-red (NIR) emitting and magnetic QDs of sizes between 3-6 nm for magnetic and fluorescent bimodal imaging are reported in this dissertation. QDs are semiconducting materials that exhibit quantum confinement with sizes below the excitonic Bohr radius of the material. NIR emitting QDs have potential to act as excellent probes for non-invasive monitoring of biological processes because NIR photons permit deep tissue penetration due to low absorption by water and other tissue components and also due to minimum tissue autofluorescence in the NIR wavelength regime of 700 -- 900 nm. QDs synthesized by the conventional organometallic route require surface modifications with hydrophilic ligands to enable dispersion in aqueous biological conditions. However, these procedures result in significant reduction in their optical properties such as quantum yields (QYs). In this research 3-6 nm alloyed QDs were synthesized by heating the precursor solutions at 180°C for various time intervals (30 -- 100 min) under hydrothermal conditions. No separate ligand exchange steps for the QDs were necessary for water dispersibility. NIR emission tunability was achieved by modifying the sizes of the QDs and also by developing a CdS rich shell on core CdTeS QDs. The alloy core and core/shell structure of the QDs were characterized using TEM, XRD, Energy dispersive X-ray spectroscopy (EDS) and XPS. The functionalization of the QDs with a non-toxic N-Acetyl-Cysteine (NAC) creates surface carboxylic acid groups which also allow subsequent bio-conjugation for targeted delivery. The QDs exhibited fluorescence in the visible-NIR 530-820 nm range and yielded high photoluminescence QYs with the maximum being about 60%. The functionality of the QDs was evaluated using in vitro mouse phantom experiments. The 800 nm emitting core/shell QDs exhibited bright photoluminescence inside the mouse phantom when excited with NIR light (710 -- 745 nm) in the Xenogen IVISRTM Spectrum Biophotonic Imager indicating their viability as NIR contrast agents.;In order to produce QDs that could also be traced by magnetic resonance imaging (MRI) the synthesis route was modified to develop novel magnetic QDs. This was achieved by controlled doping of the CdTeS QDs with Fe. Bimodal contrast agents with optical and magnetic properties integrated into one single nanoparticle (NP) resulted in a group of new materials that can be utilized in two highly complementary imaging techniques viz. fluorescence imaging and MRI. The fluorescent and magnetic Fe doped CdTeS QDs were characterized by superconducting Quantum interference device (SQUID) and MRI measurements. Fe doped QDs emitting between 530-740 nm exhibited QY within 40-60%. The saturation magnetization (Ms) values for QDs emitting at 740 nm and 730 nm were measured to be 2.8 emu/gm and 1.7 emu/gm, respectively, at room temperature. The relaxivity coefficient of the Fe doped QD emitting at 740 nm (732.4 mM-1s-1) was determined to be 88% higher than that for FeridexRTM I.V. (389.2 mM-1s-1), a commercial magnetic contrast agent (now withdrawn). The performance of the magnetic QDs was determined by in vitro labeling with J774 macrophages. In vivo experiments were also performed by injecting QD labeled macrophages into the leg muscle of mouse followed by whole animal fluorescence imaging and MRI. Significant fluorescence and magnetic contrasts were generated by the QDs with respect to the neighboring tissues inside the animal. These 3-6 nm QDs because of their small size can be cleared from the blood circulation in a short time span. The magnetic QDs have significant potential as biological contrast agents because of their dual fluorescent and magnetic properties in addition to their small size.