@article{KurokiTchoupaHartliebetal.2019, author = {Kuroki, Agnes and Tchoupa, Arnaud Kengmo and Hartlieb, Matthias and Peltier, Raoul and Locock, Katherine E. S. and Unnikrishnan, Meera and Perrier, Sebastien}, title = {Targeting intracellular, multi-drug resistant Staphylococcus aureus with guanidinium polymers by elucidating the structure-activity relationship}, series = {Biomaterials : biomaterials reviews online}, volume = {217}, journal = {Biomaterials : biomaterials reviews online}, publisher = {Elsevier}, address = {Oxford}, issn = {0142-9612}, doi = {10.1016/j.biomaterials.2019.119249}, pages = {13}, year = {2019}, abstract = {Intracellular persistence of bacteria represents a clinical challenge as bacteria can thrive in an environment protected from antibiotics and immune responses. Novel targeting strategies are critical in tackling antibiotic resistant infections. Synthetic antimicrobial peptides (SAMPs) are interesting candidates as they exhibit a very high antimicrobial activity. We first compared the activity of a library of ammonium and guanidinium polymers with different sequences (statistical, tetrablock and diblock) synthesized by RAFT polymerization against methicillin-resistant S. aureus (MRSA) and methicillin-sensitive strains (MSSA). As the guanidinium SAMPs were the most potent, they were used to treat intracellular S. aureus in keratinocytes. The diblock structure was the most active, reducing the amount of intracellular MSSA and MRSA by two-fold. We present here a potential treatment for intracellular, multi-drug resistant bacteria, using a simple and scalable strategy.}, language = {en} } @article{HartliebCatrouilletKurokietal.2019, author = {Hartlieb, Matthias and Catrouillet, Sylvain and Kuroki, Agnes and Sanchez-Cano, Carlos and Peltier, Raoul and Perrier, Sebastien}, title = {Stimuli-responsive membrane activity of cyclic-peptide-polymer conjugates}, series = {Chemical science}, volume = {10}, journal = {Chemical science}, number = {21}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {2041-6520}, doi = {10.1039/c9sc00756c}, pages = {5476 -- 5483}, year = {2019}, abstract = {Cyclic peptide nanotubes (CPNT) consisting of an even number of amino acids with an alternating chirality are highly interesting materials in a biomedical context due to their ability to insert themselves into cellular membranes. However, unwanted unspecific interactions between CPNT and non-targeted cell membranes are a major drawback. To solve this issue we have synthetized a series of CPNT-polymer conjugates with a cleavable covalent connection between macromolecule and peptide. As a result, the polymers form a stabilizing and shielding shell around the nanotube that can be cleaved on demand to generate membrane active CPNT from non-active conjugates. This approach enables us to control the stacking and lateral aggregation of these materials, thus leading to stimuli responsive membrane activity. Moreover, upon activation, the systems can be adjusted to form nanotubes with an increased length instead of aggregates. We were able to study the dynamics of these systems in detail and prove the concept of stimuli responsive membrane interaction using CPNT-polymer conjugates to permeabilize liposomes as well as mammalian cell membranes.}, language = {en} } @article{HartliebMansfieldPerrier2020, author = {Hartlieb, Matthias and Mansfield, Edward D. H. and Perrier, Sebastien}, title = {A guide to supramolecular polymerizations}, series = {Polymer Chemistry}, volume = {11}, journal = {Polymer Chemistry}, number = {6}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1759-9954}, doi = {10.1039/c9py01342c}, pages = {1083 -- 1110}, year = {2020}, abstract = {Supramolecular polymers or fibers are non-covalent assemblies of unimeric building blocks connected by secondary interactions such as hydrogen bonds or pi-pi interactions. Such structures hold enormous potential in the development of future materials, as their non-covalent nature makes them highly modular and adaptive. Within this review we aim to provide a broad overview over the area of linear supramolecular polymers including the different mechanisms of their polymerization as well as methods essential for their characterization. The different non-covalent interactions able to form supramolecular polymers are discussed, and key examples for each species are shown. Particular emphasis is laid on the development of living supramolecular polymerization able to produce fibers with a controlled length and low length dispersity, and even enable the production of supramolecular block copolymers. Another important and very recent field is the development of out-of-equilibrium supramolecular polymers, where the polymerization process can be temporally controlled enabling access to highly adaptive materials.}, language = {en} } @article{LaroqueReifarthSperlingetal.2020, author = {Laroque, Sophie and Reifarth, Martin and Sperling, Marcel and Kersting, Sebastian and Kloepzig, Stefanie and Budach, Patrick and Hartlieb, Matthias and Storsberg, Joachim}, title = {Impact of multivalence and self-assembly in the design of polymeric antimicrobial peptide mimics}, series = {ACS applied materials \& interfaces}, volume = {12}, journal = {ACS applied materials \& interfaces}, number = {27}, publisher = {American Chemical Society}, address = {Washington}, issn = {1944-8244}, doi = {10.1021/acsami.0c05944}, pages = {30052 -- 30065}, year = {2020}, abstract = {Antimicrobial resistance is an increasingly serious challenge for public health and could result in dramatic negative consequences for the health care sector during the next decades. To solve this problem, antibacterial materials that are unsusceptible toward the development of bacterial resistance are a promising branch of research. In this work, a new type of polymeric antimicrobial peptide mimic featuring a bottlebrush architecture is developed, using a combination of reversible addition-fragmentation chain transfer (RAFT) polymerization and ring-opening metathesis polymerization (ROMP). This approach enables multivalent presentation of antimicrobial subunits resulting in improved bioactivity and an increased hemocompatibility, boosting the selectivity of these materials for bacterial cells. Direct probing of membrane integrity of treated bacteria revealed highly potent membrane disruption caused by bottlebrush copolymers. Multivalent bottlebrush copolymers clearly outperformed their linear equivalents regarding bioactivity and selectivity. The effect of segmentation of cationic and hydrophobic subunits within bottle brushes was probed using heterograft copolymers. These materials were found to self-assemble under physiological conditions, which reduced their antibacterial activity, highlighting the importance of precise structural control for such applications. To the best of our knowledge, this is the first example to demonstrate the positive impact of multivalence, generated by a bottlebrush topology in polymeric antimicrobial peptide mimics, making these polymers a highly promising material platform for the design of new bactericidal systems.}, language = {en} } @article{AkarsuGrobeNowaczyketal.2021, author = {Akarsu, Pinar and Grobe, Richard and Nowaczyk, Julius and Hartlieb, Matthias and Reinicke, Stefan and B{\"o}ker, Alexander and Sperling, Marcel and Reifarth, Martin}, title = {Solid-phase microcontact printing for precise patterning of rough surfaces}, series = {ACS applied polymer materials}, volume = {3}, journal = {ACS applied polymer materials}, number = {5}, publisher = {American Chemical Society}, address = {Washington}, issn = {2637-6105}, doi = {10.1021/acsapm.1c00024}, pages = {2420 -- 2431}, year = {2021}, abstract = {We present a microcontact printing (mu CP) routine suitable to introduce defined (sub-) microscale patterns on surface substrates exhibiting a high capillary activity and receptive to a silane-based chemistry. This is achieved by transferring functional trivalent alkoxysilanes, such as (3-aminopropyl)-triethoxysilane (APTES) as a low-molecular weight ink via reversible covalent attachment to polymer brushes grafted from elastomeric polydimethylsiloxane (PDMS) stamps. The brushes consist of poly{N-[tris(hydroxymethyl)-methyl]acrylamide} (PTrisAAm) synthesized by reversible addition-fragmentation chain-transfer (RAFT)-polymerization and used for immobilization of the alkoxysilane-based ink by substituting the alkoxy moieties with polymer-bound hydroxyl groups. Upon physical contact of the silane-carrying polymers with surfaces, the conjugated silane transfers to the substrate, thus completely suppressing ink-flow and, in turn, maximizing printing accuracy even for otherwise not addressable substrate topographies. We provide a concisely conducted investigation on polymer brush formation using atomic force microscopy (AFM) and ellipsometry as well as ink immobilization utilizing two-dimensional proton nuclear Overhauser enhancement spectroscopy (H-1-H-1-NOESY-NMR). We analyze the mu CP process by printing onto Si-wafers and show how even distinctively rough surfaces can be addressed, which otherwise represent particularly challenging substrates.}, language = {en} } @article{Hartlieb2022, author = {Hartlieb, Matthias}, title = {Photo-iniferter RAFT polymerization}, series = {Macromolecular rapid communications : publishing the newsletters of the European Polymer Federation}, volume = {43}, journal = {Macromolecular rapid communications : publishing the newsletters of the European Polymer Federation}, number = {1}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1521-3927}, doi = {10.1002/marc.202100514}, pages = {25}, year = {2022}, abstract = {Light-mediated polymerization techniques offer distinct advantages over polymerization reactions fueled by thermal energy, such as high spatial and temporal control as well as the possibility to work under mild reaction conditions. Reversible addition-fragmentation chain-transfer (RAFT) polymerization is a highly versatile radical polymerization method that can be utilized to control a variety of monomers and produce a vast number of complex macromolecular structures. The use of light to drive a RAFT-polymerization is possible via multiple routes. Besides the use of photo-initiators, or photo-catalysts, the direct activation of the chain transfer agent controlling the RAFT process in a photo-iniferter (PI) process is an elegant way to initiate and control polymerization reactions. Within this review, PI-RAFT polymerization and its advantages over the conventional RAFT process are discussed in detail.}, language = {en} } @article{FloydSongHapeshietal.2022, author = {Floyd, Thomas G. and Song, Ji-Inn and Hapeshi, Alexia and Laroque, Sophie and Hartlieb, Matthias and Perrier, Sebastien}, title = {Bottlebrush copolymers for gene delivery: influence of architecture, charge density, and backbone length on transfection efficiency}, series = {Journal of materials chemistry : B, materials for biology and medicine}, volume = {10}, journal = {Journal of materials chemistry : B, materials for biology and medicine}, number = {19}, publisher = {Royal Society of Chemistry}, address = {London [u.a.]}, issn = {2050-750X}, doi = {10.1039/d2tb00490a}, pages = {3696 -- 3704}, year = {2022}, abstract = {The influence of polymer architecture of polycations on their ability to transfect mammalian cells is probed. Polymer bottle brushes with grafts made from partially hydrolysed poly(2-ethyl-2-oxazoline) are used while varying the length of the polymer backbone as well as the degree of hydrolysis (cationic charge content). Polyplex formation is investigated via gel electrophoresis, dye-displacement and dynamic light scattering. Bottle brushes show a superior ability to complex pDNA when compared to linear copolymers. Also, nucleic acid release was found to be improved by a graft architecture. Polyplexes based on bottle brush copolymers showed an elongated shape in transmission electron microscopy images. The cytotoxicity against mammalian cells is drastically reduced when a graft architecture is used instead of linear copolymers. Moreover, the best-performing bottle brush copolymer showed a transfection ability comparable with that of linear poly(ethylenimine), the gold standard of polymeric transfection agents, which is used as positive control. In combination with their markedly lowered cytotoxicity, cationic bottle brush copolymers are therefore shown to be a highly promising class of gene delivery vectors.}, language = {en} } @article{BapolisiKielbBekiretal.2022, author = {Bapolisi, Alain Murhimalika and Kielb, Patrycja and Bekir, Marek and Lehnen, Anne-Catherine and Radon, Christin and Laroque, Sophie and Wendler, Petra and M{\"u}ller-Werkmeister, Henrike and Hartlieb, Matthias}, title = {Antimicrobial polymers of linear and bottlebrush architecture}, series = {Macromolecular rapid communications : publishing the newsletters of the European Polymer Federation}, volume = {43}, journal = {Macromolecular rapid communications : publishing the newsletters of the European Polymer Federation}, number = {19}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1521-3927}, doi = {10.1002/marc.202200288}, pages = {14}, year = {2022}, abstract = {Polymeric antimicrobial peptide mimics are a promising alternative for the future management of the daunting problems associated with antimicrobial resistance. However, the development of successful antimicrobial polymers (APs) requires careful control of factors such as amphiphilic balance, molecular weight, dispersity, sequence, and architecture. While most of the earlier developed APs focus on random linear copolymers, the development of APs with advanced architectures proves to be more potent. It is recently developed multivalent bottlebrush APs with improved antibacterial and hemocompatibility profiles, outperforming their linear counterparts. Understanding the rationale behind the outstanding biological activity of these newly developed antimicrobials is vital to further improving their performance. This work investigates the physicochemical properties governing the differences in activity between linear and bottlebrush architectures using various spectroscopic and microscopic techniques. Linear copolymers are more solvated, thermo-responsive, and possess facial amphiphilicity resulting in random aggregations when interacting with liposomes mimicking Escheria coli membranes. The bottlebrush copolymers adopt a more stable secondary conformation in aqueous solution in comparison to linear copolymers, conferring rapid and more specific binding mechanism to membranes. The advantageous physicochemical properties of the bottlebrush topology seem to be a determinant factor in the activity of these promising APs.}, language = {en} } @article{ReifarthBekirBapolisietal.2022, author = {Reifarth, Martin and Bekir, Marek and Bapolisi, Alain M. and Titov, Evgenii and Nusshardt, Fabian and Nowaczyk, Julius and Grigoriev, Dmitry and Sharma, Anjali and Saalfrank, Peter and Santer, Svetlana and Hartlieb, Matthias and B{\"o}ker, Alexander}, title = {A dual pH- and light-responsive spiropyrane-based surfactant}, series = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition}, volume = {61}, journal = {Angewandte Chemie : a journal of the Gesellschaft Deutscher Chemiker ; International edition}, number = {21}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1433-7851}, doi = {10.1002/anie.202114687}, pages = {10}, year = {2022}, abstract = {A cationic surfactant containing a spiropyrane unit is prepared exhibiting a dual-responsive adjustability of its surface-active characteristics. The switching mechanism of the system relies on the reversible conversion of the non-ionic spiropyrane (SP) to a zwitterionic merocyanine (MC) and can be controlled by adjusting the pH value and via light, resulting in a pH-dependent photoactivity: While the compound possesses a pronounced difference in surface activity between both forms under acidic conditions, this behavior is suppressed at a neutral pH level. The underlying switching processes are investigated in detail, and a thermodynamic explanation based on a combination of theoretical and experimental results is provided. This complex stimuli-responsive behavior enables remote-control of colloidal systems. To demonstrate its applicability, the surfactant is utilized for the pH-dependent manipulation of oil-in-water emulsions.}, language = {en} }