A5034323485- RNA Interference and Gene Delivery
- Nanoparticle-Based Drug Delivery
- Immunotherapy and Immune Responses
- Advanced Polymer Synthesis and Characterization
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- Advanced biosensing and bioanalysis techniques
- Nanoplatforms for cancer theranostics
- Dendrimers and Hyperbranched Polymers
- Graphene and Nanomaterials Applications
- Liver physiology and pathology
- Immune cells in cancer
- Glycosylation and Glycoproteins Research
- biodegradable polymer synthesis and properties
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Phagocytosis and Immune Regulation
- SARS-CoV-2 and COVID-19 Research
- Bone health and treatments
- CAR-T cell therapy research
- Cancer Research and Treatments
- Advanced Drug Delivery Systems
- Supramolecular Self-Assembly in Materials
- Protein Interaction Studies and Fluorescence Analysis
- Radiopharmaceutical Chemistry and Applications
Max Planck Institute for Polymer Research
2017-2025
University of Würzburg
2022-2025
Institute of Molecular Functional Materials
2025
The University of Queensland
2024
Texas A&M University
2022
Ghent University
2015-2020
University of Applied Sciences Mainz
2016-2020
Clinical Research Organization
2020
Max Planck Society
2019
Cancer Research Institute Ghent
2016-2018
Significance The newest generation of small-molecule vaccine adjuvants aims at triggering specific receptors expressed by dendritic cells, the working horses our immune system. Unfortunately, owing to their small size, upon administration these molecules rapidly enter systemic circulation and cause inflammation. We report on a nanotechnology-based solution for this issue covalent ligation potent immunostimulatory molecule hydrogel nanoparticles. This approach allows lymph node-restricted...
Analogous to an assembly line, we employed a modular design for the high-throughput study of 1,536 structurally distinct nanoparticles with cationic cores and variable shells. This enabled elucidation complexation, internalization, delivery trends that could only be learned through evaluation large library. Using robotic automation, epoxide-functionalized block polymers were combinatorially cross-linked diverse library amines, followed by measurement molecular weight, diameter, RNA cellular...
Abstract Localized therapeutic modalities that subvert the tumor microenvironment from immune‐suppressive to pro‐immunogenic can elicit systemic antitumor immune responses induce regression of directly treated as well nontreated distal tumors. A key toward generating robust T cell is activation dendritic cells (DCs) in microenvironment. Treatment with agonists triggering various pattern recognition receptors very efficient activate DCs, yet suffers induction serious immune‐related adverse...
Oligonucleotides such as short, double-stranded RNA (siRNA) or plasmid DNA (pDNA) promise high potential in gene therapy. For pharmaceutical application, however, adequate drug carriers are required. Among various concepts progressing the market final development, nanosized hydrogel particles may serve novel transport media especially for siRNA. In this work, a new concept of synthesizing polymeric cationic nanohydrogels was developed, which offers promising strategy to complex and siRNA...
Abstract The search for vaccines that protect from severe morbidity and mortality because of infection with acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus causes disease 2019 (COVID‐19) is a race against clock virus. Here we describe an amphiphilic imidazoquinoline (IMDQ‐PEG‐CHOL) TLR7/8 adjuvant, consisting conjugated to chain end cholesterol‐poly(ethylene glycol) macromolecular amphiphile. It water‐soluble exhibits massive translocation lymph nodes upon local...
Tumor-associated macrophages (TAMs) promote the immune suppressive microenvironment inside tumors and are, therefore, considered as a promising target for next generation of cancer immunotherapies. To repolarize their phenotype into tumoricidal state, Toll-like receptor 7/8 agonist imidazoquinoline IMDQ is site-specifically quantitatively coupled to single chain antibody fragments, so-called nanobodies, targeting macrophage mannose (MMR) on TAMs. Intravenous injection these conjugates result...
The generation of specific humoral and cellular immune responses plays a pivotal role in the development effective vaccines against tumors. Especially presence antigen-specific, cytotoxic T cells influences outcome therapeutic cancer vaccinations. Different strategies, ranging from delivering antigen-encoding mRNAs to peptides or full antigens, are accessible but often suffer insufficient immunogenicity require immune-boosting adjuvants as well carrier platforms ensure stability adequate...
Abstract Hemiacetal esters are versatile functional groups known for their unique ability to degrade under mild conditions such as exposure water, alcohols, organic acids, or heat. In this study, hemiacetal introduced mild, transient protecting carboxylic acids along polycarbonate backbones. A six‐membered cyclic carbonate monomer is synthesized by reacting ethyl vinyl ether with a acid precursor, demonstrating high efficiency and stability nucleophilic polymerization conditions. Potential...
Highly decorated: Tumor-associated MUC1 glycopeptide and tetanus toxoid T-cell epitope P2 can be attached to water-soluble poly(N-(2-hydroxypropyl)methacrylamide) carriers by orthogonal ligation techniques. Fully synthetic vaccine A with additional nanostructure-promoting domains induced antibodies that exhibit high affinity tumor cells.
We report on the design of glycosylated nanogels via core-cross-linking amphiphilic non-water-soluble block copolymers composed an acetylated and a pentafluorophenyl (PFP) activated ester prepared by reversible addition-fragmentation (RAFT) polymerization. Self-assembly, pH-sensitive core-cross-linking, removal remaining PFP esters protecting groups are achieved in one pot yield fully hydrated sub-100 nm nanogels. Using cell subsets that exhibit high low expression mannose receptor (MR)...
Abstract We report on the design of a polymeric prodrug anticancer agent paclitaxel (PTX) by grafting‐from‐drug approach. A chain transfer for reversible addition fragmentation (RAFT) polymerization was efficiently and regioselectively linked to C2′ position paclitaxel, which is crucial its bioactivity. Subsequent RAFT hydrophilic monomer yielded well‐defined paclitaxel–polymer conjugates with high drug loading, water solubility, stability. The versatility this approach further demonstrated...
Tumor-associated macrophages (TAMs) with high expression levels of the Macrophage Mannose Receptor (MMR, CD206) exhibit a strong angiogenic and immune suppressive activity. Thus, they are highly attractive target in cancer immunotherapy, aim to modulate their protumoral behavior. Here, we introduce polymer nanogels as potential drug nanocarriers which were site-specifically decorated Nanobody (Nb) specific for MMR. Using azide-functionalized RAFT chain transfer agents, provide access...
Small molecule immuno-modulators such as agonists of Toll-like receptors (TLRs) are attractive compounds to stimulate innate immune cells toward potent antiviral and antitumor responses. However, small molecules rapidly enter the systemic circulation cause "wasted inflammation". Hence, synthetic strategies confine their radius action lymphoid tissue great relevance, both enhance efficacy concomitantly limit toxicity. Here, we demonstrate that covalent conjugation a TLR7/8 agonist...
Uncontrolled systemic inflammatory immune triggering has hampered the clinical translation of several classes small-molecule immunomodulators, such as imidazoquinoline TLR7/8 agonists for vaccine design and cancer immunotherapy. By taking advantage inherent serum-protein-binding property lipid motifs their tendency to accumulate in lymphoid tissue, we designed amphiphilic lipid-polymer conjugates that suppress inflammation but provoke potent lymph-node activation. This work provides a...
Nanostructures derived from amphiphilic DNA-polymer conjugates have emerged prominently due to their rich self-assembly behavior; however, synthesis is traditionally challenging. Here, we report a novel platform technology towards nanostructures of various shapes by leveraging polymerization-induced (PISA) for polymerization single-stranded DNA (ssDNA). A "grafting from" protocol thermal RAFT ssDNA under ambient conditions was developed and utilized the functional DNA-diblock acrylates...
Small-molecular Toll-like receptor 7/8 (TLR7/8) agonists hold promise as immune modulators for a variety of therapeutic purposes including cancer therapy or vaccination. However, due to their rapid systemic distribution causing difficult-to-control inflammatory off-target effects, application is still problematic, in particular systemically. To address this problem, we designed and robustly fabricated pH-responsive nanogels serving versatile immunodrug nanocarriers safe delivery...
Despite considerable progress in the design of multifunctionalized nanoparticles (NPs) that selectively target specific cell types, their systemic application often results unwanted liver accumulation. The exact mechanisms for this general observation are still unclear. Here we asked whether number cell-targeting antibodies per NP determines extent accumulation and also addressed by which antibody-coated NPs retained liver. We used polysarcosine-based peptobrushes (PBs), an unmodified form...
For systemic siRNA delivery applications, well-defined drug carriers are required that guarantee stability for both carrier and cargo. Among various concepts progressing in market or final development, cationic nanohydrogel particles may serve as novel transport media especially designed siRNA-in vivo experiments. In this work, the interaction of with proteins serum components was studied via dynamic light scattering human blood screening method prior to applications vivo. The formation...
To overcome the poor pharmacokinetic conditions of short double-stranded RNA molecules in interference therapies, cationic nanohydrogel particles can be considered as alternative safe and stable carriers for oligonucleotide delivery. For understanding key parameters during this process, two different types well-defined were synthesized, which provided nearly identical physicochemical properties with regards to their material composition resulting siRNA loading characteristics. Yet, according...
Poly[N-(2-hydroxypropyl) methacrylamide] (HPMA) was one of the first polymers applied as polymer drug conjugate in clinics. Since then many attempts have been made to expand functionality HPMA-based copolymers from advanced synthetic pathways multiple biomedical applications. This Feature Article highlights multifunctional HPMA based prepared by controlled radical polymerization and subsequent post-polymerization modification activated ester precursor via aminolysis. approach combines...