Self assembling block copolymers : a versatile tool for creating functional 3D and planar membranes

Driven by self assembly, amphiphilic block copolymers can be used as the basis for the creation of various artificial nano and micro-devices which can: i) deliver therapeutic agents ii) imitate functionalities found in nature and thus give us the opportunity to study and understand them iii) be engineered for biosensing and bioanalytical applications. Highlighting the versatility of block copolymers, this work describes how we can use amphiphilic block copolymers as a to assemble nanometer-sized vesicles i.e., polymersomes for reactive oxygen species (ROS) delivery in vitro, and solid supporting polymer membranes for the development of an applicable platform.
First, we used polymersomes to deliver ROS in vitro, in a controlled and biocompatible manner. A water-soluble porphyrin, which generates ROS upon irradiation under red LED light, was encapsulated in the aqueous cavity of polymersomes. The porphyrin-incorporating polymersomes were then co-cultured with Escherichia coli bacteria and three different mammalian cells lines (HeLa, HEK293T and HepG2). Next, they were irradiated to in situ photoactivate the prophryrin to produce ROS. The evaluation of our experimental findings allowed us to optimize the encapsulation and process and most importantly to find out that the polymer membrane has many valuable advantages for our system. More specifically, the low permeability of the polymer membrane limits the intrinsic toxicity of the porphyrin. At the same time, the encapsulation prolongs the ROS generation within cells. Furthermore, the ROS delivery is ’on-demand’ and only occurs upon irradiation. The following significant decrease of viability for both bacteria and mammalian cells in vitro was verified by corresponding viability assays as well as EPR spectroscopy and confocal laser microscopy. The triggerable ROS generating polymersomes proved to be promising nano-carriers for photodynamic therapy.
The second part of this thesis moves from 3D polymersomes based on poly(dimethylsiloxane)-poly(2-methyl-2-oxazoline) (PDMS-PMOXA) amphiphilic triblock copolymers to their planar counterpart. Creating a solid supported polymer membrane by using the vesicle fusion method is established for phospholipids but not for polymersomes. In order to overcome this challenge, we propose a simple procedure for creating planar polymer membranes. Here, it’s worth to mention that polymersomes are known to have a robust yet flexible outer membrane which makes their transition from hollow spherical to planar structures a demanding task. We decided to use thiol-modified polymersomes to facilitate their adsorption onto a gold coated surface. Then, we triggered the rupture of the polymersomes and the corresponding membrane formation via Ca 2+ induced osmotic shock. Using sensitive surface characterization techniques such quartz crystal microbalance with dissipation (QCM-D) monitoring, atomic force microscopy (AFM), spectroscopic ellipsometry and brewster angle microscopy (BAM) we gained a deeper understanding of polymer membrane formation requirements. Our findings suggest that i) the length of the single polymer chains and the resulting membrane thickness, ii) the attachment on solid support and iii) the external stimulus for the membrane formation have to be considered as crucial parameters. These results open up new perspectives on the creation of block copolymer based, cellular membrane-mimicking platforms.