Gold-silica quantum rattles for cancer therapy and diagnosis

The Holy Grail of cancer research is to find effective treatments that can be easily delivered to diseased cells with minimal collateral damage to healthy tissue. In this context, recent developments in nanoparticle technology have aroused considerable interest with the promise of multifunctional vectors for both diagnostic and treatment of cancer. Recently, new emphasis has been placed on hybrid nanoparticle (NP) systems, where combinations of different types of nanostructured materials are used to create multimodal systems that exhibit the combined beneficial properties of the component modules. In particular, nanorattles, which are NPs with a core-shell structure containing a distinctive void separating the core material from the shell, constitute promising launch platforms for many biomedical applications. Current hybrid NP systems tend to concentrate on adding extra properties by increasing the number of modules and therefore, system complexity. However, added complexity in itself does not guarantee higher effectiveness. Therefore, in this thesis, a more holistic approach is proposed whereby simplicity, efficiency and usefulness of the design are not overlooked. The work presented here describes a gold-silica rattle-type particle, the Quantum Rattle (QR), made of a hollow mesoporous silica shell (HS) hosting two classes of hydrophobic gold nanostructures: gold quantum dots (AuQDs) and gold nanoparticles (AuNPs). The HS stabilises the gold nanostructures, making them dispersible in water and thereby enables biomedical applications. It also allows passive targeting for the QR via the enhanced permeability and retention (EPR) effect. The AuQDs absorb and emit light in the near-infrared (NIR) biological window where blood and soft tissue are relatively transparent (650 nm - 900 nm). With their NIR photonics, the AuQDs mediate both photothermal therapy (PPT) and live infrared imaging. Finally, the hydrophobic AuNPs optimise the system’s drug carrying performance by increasing the payload’s loading efficiency as well as controlling its release profile. This thesis exhibits the first evidence of the intrinsic and efficient therapeutic and diagnostic potential of this new class of hybrid NP system and discusses how these results could have a significant impact on the growing field of nanosystems used for cancer treatment.