From Molecular Biology to Responsive Polymeric Nanocarriers

Polymeric nanoparticles and nanogels are potential carriers for the loading and release of functional compounds and represent a highly versatile concept that is experiencing a growing interest in the biomedical field. Here, combining so called “smart” stimuli-responsive polymeric nano-structures with pharmaceutically active substances is being more and more exploited for the targeted delivery of drugs and is believed to be one of the key approaches for future therapeutics.

  Therefore, developing new efficient materials in this area represents a highly desirable, but also rather complex task. It requires the effective combination of different methodologies and techniques from across a multitude of disciplines. Consequently, a successful design of (stimuli-responsive) drug delivery systems allows tuning release profiles via the adjustment of the molecular building blocks and the resulting polymeric nano-structure. In addition, the capability to predict and optimize its specific interaction with intricate biological systems has to be ensured.

    In the Klinger Lab, we approach all these challenges in a systematic way: At first, we focus on translating a (molecular) understanding of targeted biological processes to the design of synthetic response mechanisms. This can include the identification of a certain biological trigger and the development of a chemical transformation/reaction that allows using this trigger for the release of a specific compound. Second, we impart these response mechanisms into macromolecular building blocks that can ultimately be used to build up functional nanocarriers as new therapeutic agents.

    In a contrary approach, we work on the development of modular nanoparticles that can easily be modified to give a selection of carriers with distinct structural characteristics. Such a collection will allow screening of structure-property relationships in a systemic way. Ultimately, this will enable a deeper understanding of the interactions with the targeted biological systems.


Selected Publications

    [12] C. Biglione, T. M. P. Neumann-Tran, S. Kanwal, D. Klinger*

    Amphiphilic micro- and nanogels: Combining properties from internal hydrogel networks, solid         
    particles, and micellar aggregates

    J. Polym. Sci2021, 59, 2665


    Review Article

     [11] A. Gruber, A. A. Joshi, P. Graff, J. L. Cuéllar- Camacho, S. Hedtrich, D. Klinger*

      Influence of Nanogel Amphiphilicity on Dermal Delivery: Balancing Surface Hydrophobicity and         Network Rigidity

      Biomacromolecules 2022, 23, 112

      [10]  D. Işık, A. A. Joshi, X. Guo, F. Rancan, A. Klossek, A. Vogt, E. Rühl, S. Hedtrich, D. Klinger

        Sulfoxide-functionalized nanogels inspired by the skin penetration properties of DMSO

        Biomater. Sci2020, DOI: 10.1039/d0bm01717e

[09]  A. Thünemann, A. Gruber, D. Klinger

        Amphiphilic Nanogels: Fuzzy Spheres with a Pseudo-Periodic Internal Structure

        Langmuir, 2020, 36 (37), 10979

[08] T. Bewersdorff, A. Gruber, M. Eravci, M. Dumbani, D. Klinger, A. Haase

        Amphiphilic nanogels: influence of surface hydrophobicity on protein corona,
        biocompatibility and cellular uptake

        Int. J. Nanomedicine 2019, 14, 7861 

[07] A. Gruber, L. Navarro, D. Klinger

        Reactive Precursor Particles as Synthetic Platform for the Generation of
        Functional Nanoparticles, Nanogels, and Microgels

        Adv. Mater. Interf. 2020, 7, 1901676


               Review Article

[06]  A. Gruber, D. Işık, B. B. Fontanezi, C. Böttcher, M. Schäfer-Korting, D. Klinger

        A versatile synthetic platform for amphiphilic nanogels with tunable hydrophobicity

        Polym. Chem. 2018, 9, 5572

              - featured on the cover of the respective issue

       [05] C. X. Wang, S. Utech, J. D. Gopez, M. F. J. Mabesoone, C. J. Hawker, D. Klinger
               Non-Covalent Microgel Particles Containing Functional Payloads: Coacervation of
               PEG-Based Triblocks in Microfluidics

               ACS Appl. Mater. Interf. 2016, DOI: 10.1021/acsami.6b03356


[04] C. Fleischmann, J. Gopez, P. Lundberg, H. Ritter, K. L. Killops, C. J. Hawker, D. Klinger

 A Robust Platform for Functional Microgels via Thiol-Ene Chemistry with Reactive   
 Polyether-Based Nanoparticles

               Polym. Chem. 2015, 6, 2029


[03] D. Klinger and K. Landfester

Stimuli-Responsive Microgels for the Loading and Release of Functional Compounds:

Fundamental Concepts and Applications

Polymer 2012, 53, 5209


[02] D. Klinger and K. Landfester

Dual Stimuli-Responsive Poly(2-hydroxyethyl methacrylate-co-methacrylic acid) Microgels Based on Photo-Cleavable Cross-Linkers: pH-Dependent Swelling and Light-Induced Degradation

Macromolecules 2011, 44 (24), 9758

[01] D. Klinger and K. Landfester

Enzymatic- and Light-Degradable Hybrid Nanogels: Crosslinking of Polyacrylamide with Acrylate-Functionalized Dextrans Containing Photocleavable Linkers

J. Polym. Sci.: Part A Polym. Chem. 2012, 50 (6), 1062