Oncology Abstracts

We have recently discovered that metals which coordinate with selected compounds can be prepared inside liposomes. This technology, which we refer to as Metaplex™ technology, is enabling development of a brand new class of therapeutics. Previously the development of metal drug complexes (CDCs) has been hindered because of their very poor aqueous solubility. As an example, diethyldithiocarbamate (DDC) is the primary metabolite of disulfiram, an approved drug for the treatment of alcoholism that is being repurposed for cancer. The anticancer activity of DDC is dependent on complexation with copper to form copper bis-diethyldithiocarbamate (Cu(DDC)₂), a highly insoluble complex that has not been possible to develop for indications requiring parenteral administration. This issue has been resolved by preparing Cu(DDC)₂ in the presence of pre-formed liposomes. DDC reacts with copper; a reaction that can be observed through a colour change as the solution goes from a light blue to dark brown. In the absence of liposomes the complex precipitates out of solution. In the presence of liposomes, the compound remains in solution. This method has now been successfully applied to other compounds with metal coordination sites including the anti-parasitic drug clioquinol, the natural product quercetin, the semi-synthetic flavonoid flavopiridol and the novel RNA polymerase/G-Quartet targeted agent CX-5461. Our method provides a simple, transformative solution enabling the development of water insoluble compounds as viable candidate anticancer drugs. Our team is now using Metaplex™ technology with the goal of developing agents capable of inducing immunogenic cell death in vivo. ICD is a form of cell death where dying tumour cells emit signals known as damage-associated molecular patterns (DAMPs), which ultimately stimulate an adaptive immune response and potentially long-term protection against tumour growth. Metaplex™ technology can be used to generate nanomedicines capable of having direct anti-proliferative activity as well as an ability to generate a lasting immune response against tumours.