Taribagil, SG; (2013) Development of Fluorescent nanoparticles “Quantum Dots” for biomedical application. Doctoral thesis , UCL (University College London).

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Abstract

Background: Quantum dots (QDs) have emerged as one of the most exciting fluorescent nanoparticles with a potential for diagnostic and therapeutic application in the field of nanomedicine. The aim of this study was to synthesize water soluble QDs; bio-conjugating these QDs with RGD peptides prior to linking the QD-conjugated peptide to cancer cells with the aim to study cytotoxicity and assess its feasibility for in vivo studies. Methods: Water soluble Cadmium Telluride (CdTe) QDs were synthesized by the reaction of cadmium chloride with sodium tellurite in the presence of buffer solution of Mercaptosuccinic acid (MSA) as a capping ligand. Water soluble red emitting QDs thus obtained were characterized using spectrophotometric analysis. These QDs revealed a wide absorption spectrum with an excitonic absorption peak of 380nm and a narrow symmetrical emission spectrum of 630nm. The size and pattern of these QDs were studied using Transmission Electron Microscopy (TEM). These nanocrystals revealed their configuration in the form of isolated crystals or clusters measuring from 5-10nm in diameter. X-ray microanalysis combined with TEM permitted analysis of the elemental configuration of these QDs. These CdTe QDs were subsequently bound to HT 29 colon cancer cells to study the interaction of QDs in vitro. As colon cancer cells over-express integrins, QDs were conjugated with RGD (Lysine) and RGD (Cysteine) peptides for the purpose of active binding with HT29 colon cancer cells. The conjugated QDs were applied to colorectal cancer cells to assess their affinity to cellular adhesion molecules. The toxicity of naked and conjugated QDs was also assessed by analyzing cell survival and cell death after exposure to C2C12 mouse skeletal muscle cells. In vivo experiment using Sprague 5 Dawley (SD) rat established feasibility of biodistribution studies with a small dose of 10μg/ml. Results: These water soluble fluorescent CdTe nanocrystals were synthesized using relatively stable precursors. It was possible to demonstrate binding of these red emitting QDs to the HT29 colon cancer cells in vitro. Significant and stable binding was noted after QDs were conjugated with RGD peptides. Toxicity assay evaluation studies suggested that both nonconjugated and conjugated QDs were nontoxic to C2C12 mouse skeletal muscle cells at a concentration of 50 μg /ml indicating that they are less toxic to normal cells, and are safe to be applied to in vivo models. Further in vivo experimentation in SD rats established feasibility for imaging sentinel lymph nodes following interdigital web space injection of QDs. Conclusions: RGD-conjugated QDs can selectively target HT29 colorectal cancer cells with low toxicity to normal muscle cells offering a potential novel detection strategy for colorectal cancer. This property can be explored for early diagnostic and therapeutic purpose by selectively targeting cancer cells. Further studies are required in an in vivo model to analyze systemic biodistribution and toxicity studies.

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