Tumor-specific targeting of polymer drug delivery systems with recombinant proteins bound via tris(nitrilotriacetic acid)

0578323 - ÚMCH 2024 RIV NL eng J - Journal Article
Pechar, Michal - Král, Vlastimil - Kracíková, Lucie - Androvič, Ladislav - Hrdá, Eliška - Pola, Robert - Pytlíková, Sára - Studenovský, Martin - Kostka, Libor - Šubr, Vladimír - Etrych, Tomáš - Kočková, Olga - Ferreira Mendes, Jessica Marianne - Fábry, Milan - Laga, Richard
Tumor-specific targeting of polymer drug delivery systems with recombinant proteins bound via tris(nitrilotriacetic acid).
International Journal of Pharmaceutics. Roč. 648, 15 December (2023), č. článku 123619. ISSN 0378-5173. E-ISSN 1873-3476
R&D Projects: GA MŠMT LX22NPO5102
Institutional support: RVO:61389013 ; RVO:61388963
Keywords : hydrophilic polymers * thermo-responsive polymers * polymer drug delivery system
OECD category: Polymer science; Biochemistry and molecular biology (UOCHB-X)
Impact factor: 5.8, year: 2022
Method of publishing: Open access
https://www.sciencedirect.com/science/article/pii/S0378517323010414?via%3Dihub

Antibody-mediated targeting is an efficient strategy to enhance the specificity and selectivity of polymer nanomedicines towards the target site, typically a tumor. However, direct covalent coupling of an antibody with a polymer usually results in a partial damage of the antibody binding site accompanied with a compromised biological activity. Here, an original solution based on well-defined non-covalent interactions between tris-nitrilotriacetic acid (trisNTA) and hexahistidine (His-tag) groups, purposefully introduced to the structure of each macromolecule, is described. Specifically, trisNTA groups were attached along the chains of a hydrophilic statistical copolymer based on N-(2-hydroxypropyl)methacrylamide (HPMA), and at the end or along the chains of thermo-responsive di-block copolymers based on N-isopropylmethacrylamide (NIPMAM) and HPMA. His-tag was incorporated to the structure of a recombinant single chain fragment of an anti-GD2 monoclonal antibody (scFv-GD2). Static and dynamic light scattering analyses confirmed that mixing of polymer with scFv-GD2 led to the formation of polymer/scFv-GD2 complexes. Those prepared from thermo-responsive polymers formed stable micelles at 37 °C. Flow cytometry and fluorescence microscopy clearly demonstrated antigen-specific binding of the prepared complexes to GD2 positive murine T-cell lymphoma cells EL-4 and human neuroblastoma cells UKF-NB3, while no interaction with GD2 negative murine fibroblast cells NIH-3T3 was observed. These non-covalent polymer protein complexes represent a new generation of highly specific actively targeted polymer therapeutics or diagnostics.
Permanent Link: https://hdl.handle.net/11104/0347753