0000000001307905
AUTHOR
Tobias A. Bauer
Core Cross-Linked Polymeric Micelles for Specific Iron Delivery: Inducing Sterile Inflammation in Macrophages.
Iron is an essential co-factor for cellular processes. In the immune system, it can activate macrophages and represents a potential therapeutic for various diseases. To specifically deliver iron to macrophages, iron oxide nanoparticles are embedded in polymeric micelles of reactive polysarcosine-block-poly(S-ethylsulfonyl-l-cysteine). Upon surface functionalization via dihydrolipoic acid, iron oxide cores act as crosslinker themselves and undergo chemoselective disulfide bond formation with the surrounding poly(S-ethylsulfonyl-l-cysteine) block, yielding glutathione-responsive core cross-linked polymeric micelles (CCPMs). When applied to primary murine and human macrophages, these nanoparti…
Photocleavable core cross-linked polymeric micelles of polypept(o)ides and ruthenium(II) complexes
Core cross-linking of polymeric micelles has been demonstrated to contribute to enhanced stability that can improve the therapeutic efficacy. Photochemistry has the potential to provide spatial resolution and on-demand drug release. In this study, light-sensitive polypyridyl-ruthenium(II) complexes were combined with polypept(o)ides for photocleavable core cross-linked polymeric micelles. Block copolymers of polysarcosine-block-poly(glutamic acid) were synthesized by ring-opening N-carboxyanhydride polymerization and modified with aromatic nitrile-groups on the glutamic acid side chain. The modified copolymers self-assembled into micelles and were cross-linked by cis-diaquabis(2,2'-bipyridi…
Secondary Structure-Driven Self-Assembly of Thiol-Reactive Polypept(o)ides
Secondary structure formation differentiates polypeptides from most of the other synthetic polymers, and the transitions from random coils to rod-like α-helices or β-sheets represent an additional parameter to direct self-assembly and the morphology of nanostructures. We investigated the influence of distinct secondary structures on the self-assembly of reactive amphiphilic polypept(o)ides. The individual morphologies can be preserved by core cross-linking via chemoselective disulfide bond formation. A series of thiol-responsive copolymers of racemic polysarcosine-block-poly(S-ethylsulfonyl-dl-cysteine) (pSar-b-p(dl)Cys), enantiopure polysarcosine-block-poly(S-ethylsulfonyl-l-cysteine) (pSa…
Targeting Cancer Chemotherapy Resistance by Precision Medicine-Driven Nanoparticle-Formulated Cisplatin.
Therapy resistance is the major cause of cancer death. As patients respond heterogeneously, precision/personalized medicine needs to be considered, including the application of nanoparticles (NPs). The success of therapeutic NPs requires to first identify clinically relevant resistance mechanisms and to define key players, followed by a rational design of biocompatible NPs capable to target resistance. Consequently, we employed a tiered experimental pipeline fromiin silico/ito analytical andiin vitro/ito overcome cisplatin resistance. First, we generated cisplatin-resistant cancer cells and used next-generation sequencing together with CRISPR/Cas9 knockout technology to identify the ion cha…
Racemic S ‐(ethylsulfonyl)‐ dl ‐cysteine N ‐Carboxyanhydrides Improve Chain Lengths and Monomer Conversion for β‐Sheet‐Controlled Ring‐Opening Polymerization
The secondary structure formation of polypeptides not only governs folding and solution self-assembly but also affects the nucleophilic ring-opening polymerization of alpha-amino acid-N-carboxyanhydrides (NCAs). Whereby helical structures are known to enhance polymerization rates, beta-sheet-like assemblies reduce the propagation rate or may even terminate chain growth by precipitation or gelation. To overcome these unfavorable properties, racemic mixtures of NCAs can be applied. In this work, racemicS-(ethylsulfonyl)-dl-cysteine NCA is investigated for the synthesis of polypeptides, diblock and triblock copolypept(o)ides. In contrast to the polymerization of stereoregularS-(ethylsulfonyl)-…
Functionalization of P3HT with Various Mono- and Multidentate Anchor Groups
Due to its favorable optoelectronic properties and the accessibility via Grignard metathesis (GRIM) polymerization, poly(3-hexylthiophene) (P3HT) is one of the most applied conjugated polymers. The ‘living' nature of GRIM polymerization enables the modification of the polymer and the installation of desired properties. In the present study, two versatile approaches for the synthesis of anchor group-modified P3HT have been developed, which enable the functionalization of various inorganic nanoparticles. Depending on the polymerization conditions, mono- and bifunctional ethynyl-terminated P3HT or solely monofunctionalized aldehyde-terminated P3HT was synthesized. Afterwards, the quantitative …