Rizvi, SB; (2012) Semiconductor Quantum Dots as fluorescent probes for cancer localisation and Sentinel Lymph Node Biopsy. Doctoral thesis , UCL (University College London).

Abstract

Quantum Dots (QDs) are fluorescent nanoparticles that can be used as fluorescent probes for cancer localisation and sentinel lymph node biopsy (SLNB). The current tracers for SLNB including the blue dye and radiocolloid have various drawbacks limiting their widespread use. Near Infrared (NIR) QDs can potentially replace these tracers, based on their deep tissue visibility as the biological window is transparent to NIR wavelengths. QDs can also be conjugated to specific biomolecules for targeted cancer localisation and therapy. Their main limitation is toxicity as most QDs are based on heavy metal salts. This project aims to develop a biocompatible QD for clinical application using a novel nanoparticle - Polyhedral Oligomeric Silsesquioxane (POSS) based surface coatings. Materials & Methods A novel nanocomposite polymer emulsion POSS-PCU was synthesized by integrating POSS units into poly(carbonate-urea)urethane (PCU) chains and used to encapsulate QDs based on CdTe/CdSe/ZnSe and CdTe/CdS/ZnS. Mercapto-POSS on its own was also used to coat CdTe core QDs. Characterization was performed using various techniques and in vitro toxicity was established. QDs were bioconjugated to anti-HER2 antibody and used to localise HER-2 receptors on SK-BR-3 breast cancer cells. In vivo biodistribution was determined using a tail vein injection of QDs into male Sprague-Dawley rats for 1 and 24h. Organ biodistribution was quantified by fluorescence studies and Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). A live NIR imaging system was set up and NIR-QDs used to demonstrate SLN localisation in a rat model. Results POSS-PCU coated QDs showed significantly reduced toxicity and enhanced photostability on in vitro and in vivo studies. QD-anti-HER2-Antibody bioconjugate successfully localised HER-2 receptors in vitro. Biodistribution studies showed maximal uptake by the liver and spleen. NIR-QDs localised to the SLN and were visualised by the live NIR imaging system. Conclusion NIR-QDs can be used as fluorescent probes for cancer localisation and SLNB. POSS nanocomposite based surface coatings can stabilise QDs for overall reduced toxicity and enhanced photostability allowing relentless possibilities for clinical application.

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