Synthesis and assembly of stimuli-responsive amphiphiles for targeted diagnostics and drug delivery

The current project aims to develop nanocarriers that possess crucial stealth properties, but which can activate their cell-targeting properties in the presence of specific stimuli. In recent decades, functional supramolecular systems have played an important role in the development of innovative materials, e.g. for drug delivery. However, such systems are known to encounter various obstacles in terms of circulation, targeting efficiency and specificity of drug release. In biomedical applications, polyethylene glycol (PEG) functionalization has been an important approach to modify nanocarriers such as liposomes, prevent phagocyte-mediated uptake and prolong their circulation time in the blood. However, this approach faces limitations relating to the high stability of the stealth liposome, which prevents specific uptake by the desired cellular target. To overcome this dilemma, this study investigates the assembly of light-cleavable PEGylated lipids, conventional phospholipids (e.g. POPC) and targeting ligands to develop stimuli-responsive stealth liposomes. Coumarin derivatives are used as a light-responsive linker connected to the hydrophobic lipid via a carbonate bond that can be irreversibly cleaved, leading to elimination of a PEG-coumarin fragment and exposure of tumor-targeting ligands on the liposome. Previously, our group investigated the self-assembly of stimuli-responsive amphiphiles to form nanovesicles and giant unilamellar vesicles. Our current aims are to explore an irreversible light-responsive approach to overcome the PEG dilemma and develop nanocarriers for applications in diagnostics, targeted delivery of therapeutics, and applications in systems chemistry such as vesicle-vesicle communication.