(Bio)macromolecular therapeutics are a cornerstone in nanomedicine for modern cancer therapy. This is due to the their high target specificity and bioactivity as well as the ease of synthetic customization to introduce various functions through chemical design. Most of these strategies are aimed at destroying cancer cells. However, it has been shown that cancer cells form only a small fraction of the total tumor volume and the tumor should be considered as a dynamically changing ecosystem. Therefore, addressing this ecosystem, i.e, the tumor microenvironment (TME), could enable more effective treatments to eradicate cancer, with the ultimate goal to prevent migration and metastasis. Our approach is to develop new chemical strategies and biopolymers that address both the cellular and physicochemical space of the TME.
Bioactive Peptides and Proteins, Site-selective Protein Conjugation, Antibody-Drug-like Conjugates, Dynamic Covalent Linkers
Marco Raabe, Astrid Heck, Siska Führer, Dominik Schauenburg, Michaela Pieszka, Tao Wang, Maksymilian Marek Zegota, Lutz Nuhn, David Y. W. Ng, Seah Ling Kuan, and Tanja Weil, "Assembly of pH-Responsive Antibody-Drug-Inspired Conjugates," Macromolecular Bioscience 22 (2), 2100299 (2022).
Maksymilian Marek Zegota, Michael Müller, Bellinda Lantzberg, Gönül Kizilsavas, Jaime A. S. Coelho, Pierpaolo Moscariello, María Martínez Negro, Svenja Morsbach, Pedro M. P. Gois, Manfred Wagner, David Y. W. Ng, Seah Ling Kuan, and Tanja Weil, "Dual Stimuli-Responsive Dynamic Covalent Peptide Tags: Toward Sequence-Controlled Release in Tumor-like Microenvironments," Journal of the American Chemical Society 143 (41), 17047-17058 (2021).
Lujuan Xu, Maria S J. S. A. Silva, Pedro Góis, Seah Ling Kuan, and Tanja Weil, "Chemoselective cysteine or disulfide modification via single atom substitution in chloromethyl acryl reagents," Chemical Science 12 (40), 13321-13330 (2021).
Maksymilian Marek Zegota, T. Wang, Christiane Seidler, David Yuen Wah Ng, Seah Ling Kuan, and Tanja Weil, ""Tag and Modify" Protein Conjugation with Dynamic Covalent Chemistry," Bioconjugate Chemistry 29 (8), 2665-2670 (2018).
Supramolecular Fusion Proteins, Multimodal Therapy, Enzyme Therapy
Image adapted from Chem. Eur. J. 2016, 22, 17112; © 2016 Wiley-VCH Verlag
Astrid Heck, Theresa Ostertag, Leonie Schnell, Stephan Fischer, Bikram Keshari Agrawalla, Pia Winterwerber, Eva Wirsching, Michael Fauler, Manfred Frick, Seah Ling Kuan, Tanja Weil, and Holger Barth, "Supramolecular Toxin Complexes for Targeted Pharmacological Modulation of Polymorphonuclear Leukocyte Functions," Advanced Healthcare Materials 8 (17), 1900665 (2019).
Seah Ling Kuan, S. Fischer, S. Hafner, T. Wang, T. Syrovets, Weina Liu, Yu Tokura, David Yuen Wah Ng, A. Riegger, C. Förtsch, D. Jäger, T. F. E. Barth, T. Simmet, H. Barth, and Tanja Weil, "Boosting Antitumor Drug Efficacy with Chemically Engineered Multidomain Proteins," Advanced Science 5 (8), 1701036 (2018).
S. L. Kuan, C. Förtsch, D. Y. W. Ng, S. Fischer, Y. Tokura, W. N. Liu, Y. Z. Wu, Kaloian Koynov, H. Barth, and Tanja Weil, "A Supramolecular Approach toward Bioinspired PAMAM-Dendronized Fusion Toxins," Macromolecular Bioscience 16 (6), 803-810 (2016).
Seah Ling Kuan, David Y. W. Ng, Yuzhou Wu, C. Förtsch, H. Barth, Mikheil Doroshenko, Kaloian Koynov, C. Meier, and Tanja Weil, "pH Responsive Janus-like Supramolecular Fusion Proteins for Functional Protein Delivery," Journal of the American Chemical Society 135 (46), 17254-17257 (2013).
"If I have seen further it is by standing on the shoulders of Giants."
― Sir Isaac Newton