Development of an Encapsulation Method for Palladium Complexes in Biodegradable Nanostructures for In-Cellulo Catalysis

Details

Supervisors

Riant, Olivier ; Gohy, Jean-François

Faculty

Faculté des sciences

Degree label

Master [120] en sciences chimiques

Abstract

The present status of cancer is still considered as one of the major causes of death worldwide. Several treatments are already being performed on patients, such as surgery, radiation therapy and chemotherapy. However, surgery is usually performed for early cancer stages and chemo and radiation therapy are not specific approaches, as they also damage surrounding healthy tissues, they induce side effects and finally, they are unable to target cancer cells that are the farthest from the bloodstream (hypoxic cells). New therapies are still being developed in order to overcome these challenges and one of them is called passive targeting. This concept is focused on the encapsulation of drugs inside of nanocarriers, that will specifically accumulate into tumors, due to the so-called enhanced permeability and retention (EPR) effect. The research group of Pr. Olivier Riant and Pr. Jean-François Gohy decided to work on this concept and to combine it with a second, recent one called Bioorthogonal chemistry. Instead of encapsulating drugs, they decided to work with Palladium complexes and to trap them inside polymeric micelles as nanocarriers, to enhance their delivery into hypoxic cancer cells by the EPR effect, without inducing any side reactions. Thus, once at target, the complex should be released, able to be activated and selectively react with an anticancer prodrug or a protected fluorophore, via a Bioorthogonal reaction called Tsuji-Trost. Therefore, in this master thesis project, we first synthetized the required Palladium complexes. Secondly, their activation mechanism and their ability to perform a Tsuji-Trost reaction to deprotect a fluorophore was studied in vitro. Finally, we developed an encapsulation method for the precatalysts to entrap them into biodegradable and biocompatible block copolymer micelles. Finally, the efficiency of those encapsulated precatalysts in in vitro trials was studied.