Design of rhodamine-gadolinium agents for theranostic applications

Abstract

The prevalence of cancer is expected to rise over the next decade, and the development of new and effective cancer treatments and diagnostic tools is urgently required. An exciting field of cancer research involves combining therapeutic and diagnostic tools into a single ‘theranostic’ platform. The role of theranostics in the personalized management of oncology patients is increasing, as is the demand for new types of theranostic agents.

This thesis investigates a series of Gd(III) complexes which utilise rhodamine-like groups to target and image the mitochondria of tumour cells. The synthesis, purification and characterisation of a series of new Gd(III)-rhodamine complexes are reported. Systematic modifications were made to both the linking groups and the rhodamine core to determine structure-activity relationships for these complexes and their fluorescent and biological properties.

Fluorescence studies were performed where absorption, emission, quantum yields, fluorescence lifetimes and pH properties were evaluated. These studies identified the role of extended delocalisation in rhodamine-like targeting groups favoring an increase in twisted intramolecular charge transfer quenching processes. These studies also showed the importance of the structural and electronic properties of the linking groups on the absorption and emission wavelengths, quantum yields and fluorescence lifetimes of the complexes in aqueous solution.

Preliminary evaluation of the biological properties of the Gd(III)-rhodamine complexes confirmed low in vitro cytotoxicity. The selectivity and uptake of the Gd(III) complexes in a healthy brain cell line (SVG p12) and glioblastoma cell line (T98G) were also determined and found to be selective for the latter at low concentrations.