Molecules Centre

Single-Chain Polymer Nanoparticles targeting Malaria in Mosquitoes

Naomi M. Hamelmann,  Jan-Willem D. Paats, Yunuen Avalos-Padilla, Elena Lantero, Inga Siden-Kiamos, Xavier Fernàndez-Busquets and Jos M. J. Paulusse

Malaria is a mosquito-borne disease and of the five parasite species, that can infect humans plasmodium falciparum is the deadliest. The eradication of malaria provides an urgent challenge as drug resistance of the parasite is growing. Controlled drug delivery offers high potential, as nanocarriers are utilized to transport therapeutics to a specific target, increasing the therapeutics efficacies. Alternatively, to targeting the parasite in humans, here we target the parasite at the ookinete state in mosquitoes avoiding the administration of therapeutics to humans. This project focuses on the use of single-chain polymer nanoparticles (SCNPs) as nanoparticles, which are formed by intramolecular crosslinking of single polymer chains forming particles with an unique size range of 5 to 20 nm. The SCNPs properties are highly dependent on the precursor polymers and control over surface modification of SCNPs provides a modular system with great potential in biomedical applications. Here, glycerol SCNPs were formed by thiol-Michael addition and the surface was modified with increasing amounts of succinic anhydride to induce negative surface charges. The ability of SCNPs to target ookinetes dependent on the surface charge was studied and the biodistribution of SCNPs in mosquitoes was analyzed. 

Extraction of Lysozyme from Chicken Albumen Using Polyelectrolyte Complexes

Jéré J. van Lente, Saskia Lindhoud

Cells use droplet-like membraneless organelles to compartmentalize and selectively take-up molecules, such as proteins, from their internal environment. These membraneless organelles can be mimicked by polyelectrolyte complexes consisting of oppositely charged polyelectrolytes. Previous research has demonstrated that protein uptake strongly depends on the polyelectrolyte complex composition. This suggests that polyelectrolyte complexes can be used to selectively extract proteins from a multi-protein mixture. With this in mind, the partitioning of the protein lysozyme in four polyelectrolyte complex systems consisting of different weak and strong polyelectrolyte combinations is investigated. All systems show similar trends in lysozyme partitioning as a function of the complex composition. The release of lysozyme from complexes at their optimal lysozyme uptake composition was investigated by increasing the salt concentration to 500 mm NaCl or lowering the pH from 7 to 4.  Complexes of poly(allylamine hydrochloride) and poly(acrylic acid)  had the best uptake and release properties. These were used for selective extraction of lysozyme from a hen-egg white protein matrix. The (back)-extracted lysozyme retained its enzymatic activity, showing the capability of polyelectrolyte complexes to function as extraction media for proteins.

Bioinspired chemical approaches to engineer crosslinked networks with tailorable properties for cell encapsulation

Minye Jin, Alisa Gläser, Supun W. Mohotti, Gülistan Koçer, Julieta I. Paez

Hydrogels are polymer networks that are used as extracellular matrix mimics in diverse biomaterials field, including 3D cell culture, drug delivery and tissue engineering. Several covalent crosslinking strategies have been described for achieving simultaneous hydrogel crosslinking, biofunctionalization and cell encapsulation. However, developing such covalent strategies, which are efficient under physiological conditions and highly tunable but without inhibiting cell function, still remains a challenge. Ideally, the coupling reaction should be non-toxic, chemically bioorthogonal, and should enable tailoring of network properties to adapt the system to different biomedical applications. Here, we introduce a hydrogel platform bioinspired on a condensation reaction between 2-cyanobenzothiazole (CB) and aminothiol (AT) group in the presence of living cells that features all these attributes. The resulting hydrogels, based on polyethylene glycol(PEG), present rapid and tunable gelation kinetics; are mechanically stable, homogeneous at the microscale, and cytocompatible. By engineering the chemical crosslinks in the hydrogel network, fine tuning of the gelation onset and kinetics is achieved, thus expanding the accessibility of this bioinspired chemistry towards clinical interest.

Reversible acetalization of cellulose: A platform for bio-based polymers with adjustable properties and full biodegradation

Stefan Peil, Hubert Gojzewski and Frederik R. Wurm

Since the 1950s, synthetic polymers have been developed and introduced in a multiplicity of applications in our modern life. Worldwide, over 350 million tons of synthetic plastics are produced annually and more than 8300 million metric tons of virgin polymers have been produced up to date. During the last years, more and more concerns about synthetic polymers have been raised because of their persistence in the environment which causes accumulating (micro)plastics litter on our planet. Therefore a shift towards bio-based and biodegradable polymers in our daily life is urgently needed

Therefore, we have investigated the acetalization of cellulose as a new class of fully reversible cellulose modifications. The acetalization reaction enables to adjust material properties and good processability, which would not possible with unmodified cellulose. Furthermore, the acetalization is fully reversible by an efficient acidic hydrolysis at 60°C which is a ubiquitous condition during composting. After hydrolysis, unmodified cellulose remains which is fully degraded by cellulase enzymes. Therefore, we believe that the acetalization of cellulose can lead to a new class of bio-based and fully biodegradable materials for a more sustainable future.