UC San Diego

Integrating a diagnostic moiety with a therapeutic payload promises improved prognoses in diseases such as cancer by simultaneously illuminating and treating cancerous tumors. However potential theranostic materials and chemicals must be biocompatible and evade rapid clearance from the body. Such strict constraints require an interdisciplinary approach to research. Working toward to address those constraints requires drawing on such disparate fields as DNA nanotechnology, Janus nanoparticle synthesis, and chemical conjugation in order to one day create a viable theranostic carrier.

Using an inosine-based partial strand displacement scheme is reported a nanoscale positioning capabilities are used to provide on-demand activation and deactivation of a pair of split E6 DNAzymes on the device. The device also demonstrates a combined catalytic rate significantly higher than the original E6 DNAzyme under similar operational conditions. This approach can provide structural organization and spatially control the opening and closing of a theranostic particle.

Janus nanoparticles (JNP) synthesis methods were pursued to create potential theranostic carriers. Two particular morphologies are explored: (i) a gold-ball like core-shell carrier and (ii) a eccentrically encapsulated JNP. For the golf-ball structure, a hierarchical template synthesis scheme was used to create a carrier consisting of (i) solid silica core with a pitted gold surface and (ii) a hollow/porous gold shell without silica. Along with the golf-ball carrier, a carrier derived eccentric encapsulation of a one material around another. Using a sol-gel synthesis method, eccentric Janus nanoparticles composed of a silica shell partially encapsulating a carboxylate-modified polystyrene core (cPS). Nano-bowl-like structures were derived after the removal of the polystyrene core by organic solvent. The role of the polystyrene core in determining the eccentric JNP morphology and size was also elucidated.

These eccentric JPs and nanobowls can be further developed to create a magnetic gold nanobowl (mGNB). Such mGNBs consisted of a silica bowl whose outer surface is coated with iron oxide/gold/PEG in that order and a exposed silica bowl interior. The nanobowls demonstrated a surface enhanced Raman spectroscopy capability, showed cellular uptake in vitro and dose-dependent toxicity. Finally, we demonstrate preliminary work toward loading a payload (fluorophore, anti-cancer prodrug) in the silica bowl.