Biodegradable NIR-active contrast agents with amplifying photoacoustic effect for cancer theranostics

This study discusses two classes of contrast agents, which can potentially be used in photoacoustic imaging and improve the early detection rate of cancer. The developed agents exhibit high adsorption in the near-infrared window (wavelength range of 700-1000 nm), high photo-stability, and efficient conversion of heat energy to produce acoustic waves. The first developed agent is comprised of gold nanoclusters. The inter-particle interactions between ~5 nm gold nanoparticles (Au NPs) were manipulated to form biodegradable, NIR-active nanoclusters. The inter-particle spacing was tuned to <1 nm within the clusters so that the surface plasmon resonance shifted to the NIR window. This was achieved by employing optimized binary ligand systems on the surface of Au NPs. The clusters were able to dissociate back to individual ~5 nm Au NPs in physiological media. This dissociation allows for the renal clearance of individual particles. In addition to Au NPs with binary ligands, another subclass of Au NP clusters was developed using glutathione (GSH) to cover the surface of the nanoparticles. The inter-particle interactions were tuned by using pH of the solution as a control knob to create and dissociate nanoclusters reversibly. The second class of contrast agents consists of organic materials that are already approved by the US Food and Drug Administration (FDA). J-aggregates of Indocyanine green (ICG) show a sharp, intense peak at a wavelength of 890 nm; however, they are not stable in physiological environment. These J-aggregates were protected by being encapsulated in poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (PEG-PLGA) nanocapsules, which show excellent stability and optimal degradation kinetics in physiological environments. Additionally, a novel coating method was developed to protect ICG J-aggregates with polyethylenimine (PEI) so that the J-aggregates maintain their form during encapsulation. The following chapters describe novel methods to synthesize biocompatible contrast agents with control over their size, stability, and degradation kinetics. These agents have the potential to be utilized in cancer theranostics