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.