Design and manufacture of functional catalyst-carrier structures for the bioorthogonal activation of anticancer agents

Abstract

Novel palladium (Pd)-loaded titanium (Ti) devices with high biocompatibility and catalytic activity were prepared using a range of fabrication methods such as powder metallurgy (i.e. sintering with and without space-holder), sputtering, pulsed laser deposition and supersonic cluster beam deposition. The surface of the Ti-[Pd] devices were physico-chemically characterised to confirm the non-alloyed state of the Pd coating onto the titanium substrate. The Pd thickness was optimised to achieve maximum surface area (i.e. maximum catalytic effect) using the minimum amount of material in each method for cost effective production. The catalytic response of the different Ti-[Pd] devices was evaluated under biocompatible conditions by employing an off-on Pd-activatable fluorescent probe. The most robust coating of Pd was produced by an optimised magnetron sputtering method. The sputtered Ti-[Pd] devices were selected to induce the bioorthogonal uncaging of the anticancer drug Vorinostat from a pharmacologically-inactive Pd-activatable precursor in cancer cell culture, demonstrating the capacity of these devices to mediate a local anti-tumour effect via in situ release of a clinically approved drug. This approach is the first step towards surgically implantable devices that could facilitate targeting affected areas with high spatial selectivity, improving pharmacological activity and reducing systemic side effects through localised treatment directly at the cancer site.