PLENARY: Biocompatible catalytic devices and bioorthogonally-activated prodrugs to mediate local chemotherapy
(presenter: Asier Unciti-Broceta)
Abstract: The goal of performing bio-independent synthetic processes in biological environments, so-called bioorthogonal chemistry, has challenged us to search for novel biocompatible reactions for the last two decades. Among the strategies developed, the introduction of abiotic metals to this field opened the possibility of producing supra-stoichiometric amounts of xenobiotics in living systems in a non-enzymatic fashion [1-5]. Based on the biocompatibility of some transition metal catalysts (e.g. Pd or Au), our lab has pioneered the use of heterogeneous catalysis to enable the site-specific “manufacture” of chemotherapeutic agents in specific anatomical locations (e.g. inside tumours). As opposed to biolabile prodrugs, whose activation process relies on metabolic pathways, an efficient bioorthogonally-activated prodrug therapy would be entirely dependent on the distinct catalytic properties of the metal and remain intact in the absence of the metal source. In this talk I will present the discovery of Pd and Au-catalyzed dealkylation reactions [1-4] that take place under biocompatible conditions and their application as masking methods to eliminate the fluorescence and bioactivity of dyes and clinically-used drugs, respectively, while enabling the bioorthogonal rescue of the compounds’ properties by metal-functionalized devices (including Pd-loaded exosomes ) in cancer cell culture, living organisms and tumours.